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 . .

TY  - JOUR
AU  - Babić, Mirjana
AU  - Veljović, Katarina
AU  - Popović, Nikola
AU  - Golić, Nataša
AU  - Radojković, Dragica
AU  - Stanković, Marija
PY  - 2023
UR  - https://doi.org/10.1093/jambio/lxad257
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2204
AB  - Chronic lung diseases are a major and increasing global health problem, commonly caused by cigarette smoke. We aimed to explore the antioxidant effects of lactic acid bacteria (LAB) against cigarette smoke in bronchial epithelial cells.The antioxidant effects of 21 heat-killed (HK) LAB strains were tested in cigarette smoke stimulated BEAS-2B cells and 3-D bronchospheres organoids. We showed that HK Lactiplantibacillus plantarum BGPKM22 possesses antioxidant activity against cigarette smoke, resistance to hydrogen peroxide, and free radical neutralizing activity. We demonstrated that HK BGPKM22 inhibited cigarette smoke induced expression of the Aryl hydrocarbon receptor (AhR) and Nuclear factor erythroid 2 related factor 2 (Nrf2) genes. The cell-free supernatant (SN) of BGPKM22 fully confirmed the effects of HK BGPKM22.For the first time, we revealed that HK and SN of L. plantarum BGPKM22 possess antioxidant activity and modulate AhR and Nrf2 gene expression in bronchial epithelial cells exposed to cigarette smoke.
T2  - Journal of Applied Microbiology
T1  - Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke
SP  - lxad257
VL  - n/a
DO  - 10.1093/jambio/lxad257
ER  - 

@article{
author = "Babić, Mirjana and Veljović, Katarina and Popović, Nikola and Golić, Nataša and Radojković, Dragica and Stanković, Marija",
year = "2023",
abstract = "Chronic lung diseases are a major and increasing global health problem, commonly caused by cigarette smoke. We aimed to explore the antioxidant effects of lactic acid bacteria (LAB) against cigarette smoke in bronchial epithelial cells.The antioxidant effects of 21 heat-killed (HK) LAB strains were tested in cigarette smoke stimulated BEAS-2B cells and 3-D bronchospheres organoids. We showed that HK Lactiplantibacillus plantarum BGPKM22 possesses antioxidant activity against cigarette smoke, resistance to hydrogen peroxide, and free radical neutralizing activity. We demonstrated that HK BGPKM22 inhibited cigarette smoke induced expression of the Aryl hydrocarbon receptor (AhR) and Nuclear factor erythroid 2 related factor 2 (Nrf2) genes. The cell-free supernatant (SN) of BGPKM22 fully confirmed the effects of HK BGPKM22.For the first time, we revealed that HK and SN of L. plantarum BGPKM22 possess antioxidant activity and modulate AhR and Nrf2 gene expression in bronchial epithelial cells exposed to cigarette smoke.",
journal = "Journal of Applied Microbiology",
title = "Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke",
pages = "lxad257",
volume = "n/a",
doi = "10.1093/jambio/lxad257"
}

Babić, M., Veljović, K., Popović, N., Golić, N., Radojković, D.,& Stanković, M.. (2023). Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke. in Journal of Applied Microbiology, n/a, lxad257.
https://doi.org/10.1093/jambio/lxad257

Babić M, Veljović K, Popović N, Golić N, Radojković D, Stanković M. Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke. in Journal of Applied Microbiology. 2023;n/a:lxad257.
doi:10.1093/jambio/lxad257 .

Babić, Mirjana, Veljović, Katarina, Popović, Nikola, Golić, Nataša, Radojković, Dragica, Stanković, Marija, "Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke" in Journal of Applied Microbiology, n/a (2023):lxad257,
https://doi.org/10.1093/jambio/lxad257 . .

TY  - JOUR
AU  - Stanković, Marija
AU  - Veljović, Katarina
AU  - Popović, Nikola
AU  - Kojić, Snežana
AU  - Dunjić Manevski, Sofija
AU  - Radojković, Dragica
AU  - Golić, Nataša
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1538
AB  - Bronchial epithelial cells are exposed to environmental influences, microbiota, and pathogens and also serve as a powerful effector that initiate and propagate inflammation by the release of proinflammatory mediators. Recent studies suggested that lung microbiota differ between inflammatory lung diseases and healthy lungs implicating their contribution in the modulation of lung immunity. Lactic acid bacteria (LAB) are natural inhabitants of healthy human lungs and also possess immunomodulatory effects, but so far, there are no studies investigating their anti-inflammatory potential in respiratory cells. In this study, we investigated immunomodulatory features of 21 natural LAB strains in lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Our results show that several LAB strains reduced the expression of pro-inflammatory cytokine and chemokine genes. We also demonstrated that two LAB strains, Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22, effectively attenuated LPS-induced nuclear factor-kappa B (NF-kappa B) nuclear translocation. Moreover, BGZLS10-17 and BGPKM22 reduced the activation of p38, extracellular signal-related kinase (ERK), and c-Jun amino-terminal kinase (JNK) signaling cascade resulting in a reduction of pro-inflammatory mediator expressions in BEAS-2B cells. Collectively, the LAB strains BGZLS10-17 and BGPKM22 exhibited anti-inflammatory effects in BEAS-2B cells and could be employed to balance immune response in lungs and replenish diminished lung microbiota in chronic lung diseases.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22 Exhibit Anti-Inflammatory Effect by Attenuation of NF-kappa B and MAPK Signaling in Human Bronchial Epithelial Cells
IS  - 10
VL  - 23
DO  - 10.3390/ijms23105547
ER  - 

@article{
author = "Stanković, Marija and Veljović, Katarina and Popović, Nikola and Kojić, Snežana and Dunjić Manevski, Sofija and Radojković, Dragica and Golić, Nataša",
year = "2022",
abstract = "Bronchial epithelial cells are exposed to environmental influences, microbiota, and pathogens and also serve as a powerful effector that initiate and propagate inflammation by the release of proinflammatory mediators. Recent studies suggested that lung microbiota differ between inflammatory lung diseases and healthy lungs implicating their contribution in the modulation of lung immunity. Lactic acid bacteria (LAB) are natural inhabitants of healthy human lungs and also possess immunomodulatory effects, but so far, there are no studies investigating their anti-inflammatory potential in respiratory cells. In this study, we investigated immunomodulatory features of 21 natural LAB strains in lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Our results show that several LAB strains reduced the expression of pro-inflammatory cytokine and chemokine genes. We also demonstrated that two LAB strains, Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22, effectively attenuated LPS-induced nuclear factor-kappa B (NF-kappa B) nuclear translocation. Moreover, BGZLS10-17 and BGPKM22 reduced the activation of p38, extracellular signal-related kinase (ERK), and c-Jun amino-terminal kinase (JNK) signaling cascade resulting in a reduction of pro-inflammatory mediator expressions in BEAS-2B cells. Collectively, the LAB strains BGZLS10-17 and BGPKM22 exhibited anti-inflammatory effects in BEAS-2B cells and could be employed to balance immune response in lungs and replenish diminished lung microbiota in chronic lung diseases.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22 Exhibit Anti-Inflammatory Effect by Attenuation of NF-kappa B and MAPK Signaling in Human Bronchial Epithelial Cells",
number = "10",
volume = "23",
doi = "10.3390/ijms23105547"
}

Stanković, M., Veljović, K., Popović, N., Kojić, S., Dunjić Manevski, S., Radojković, D.,& Golić, N.. (2022). Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22 Exhibit Anti-Inflammatory Effect by Attenuation of NF-kappa B and MAPK Signaling in Human Bronchial Epithelial Cells. in International Journal of Molecular Sciences
MDPI, Basel., 23(10).
https://doi.org/10.3390/ijms23105547

Stanković M, Veljović K, Popović N, Kojić S, Dunjić Manevski S, Radojković D, Golić N. Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22 Exhibit Anti-Inflammatory Effect by Attenuation of NF-kappa B and MAPK Signaling in Human Bronchial Epithelial Cells. in International Journal of Molecular Sciences. 2022;23(10).
doi:10.3390/ijms23105547 .

Stanković, Marija, Veljović, Katarina, Popović, Nikola, Kojić, Snežana, Dunjić Manevski, Sofija, Radojković, Dragica, Golić, Nataša, "Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22 Exhibit Anti-Inflammatory Effect by Attenuation of NF-kappa B and MAPK Signaling in Human Bronchial Epithelial Cells" in International Journal of Molecular Sciences, 23, no. 10 (2022),
https://doi.org/10.3390/ijms23105547 . .

TY  - JOUR
AU  - Rakićević, Ljiljana
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
AU  - Radojković, Milica
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1587
AB  - Uvod/Cilj Terapija kumarinima predstavlja jedan od najboljih modela za primenu farmakogenetike. Doprinos faktora koji utiču na terapiju kumarinima može značajno da varira između etničkih grupa, što opravdava sprovođenje studija specifičnih za populaciju. Cilj ove studije je bio da se analizira uticaj najvažnijih genetičkih faktora (geni VKORC1 i CYP2C9) koji utiču na terapiju kumarinima kod bolesnika iz Srbije. Metode Sprovedena je retrospektivna studija koja je obuhvatila 207 bolesnika na terapiji acenokumarolom. Genetičke analize su vršene direktnim sekvenciranjem. Analiziran je uticaj na dozu acenokumarola varijanti (VKORC1*2, CYP2C9*2, CYP2C9*3) koje izazivaju preosetljivost i varijanti gena VKORC1 koje izazivaju rezistenciju na kumarine. Višestruka regresiona analiza je korišćena u cilju dizajniranja matematičkog modela za predviđanje individualne doze leka na osnovu kliničko-demografskih i genetičkih podataka. Rezultati Studija je potvrdila značajan uticaj analiziranih genetičkih faktora na održavanje doze acenokumarola. Dizajniran je matematički model za predviđanje individualne doze acenokumarola i njegov nekorigovani R2 je bio 61,8. Prilikom testiranja, naš model je dao R2 vrednost od 42,6 i pokazao bolje predviđanje u poređenju sa modelom koji su dali drugi autori. Kod analiziranih bolesnika pronađeno je devet različitih varijanti u kodirajućem regionu gena VKORC1. Među nosiocima ovih varijanti 78% je bilo potpuno rezistentno, te nije bilo moguće postići terapeutski efekat čak ni sa visokim dozama acenokumarola. Zaključci Populacioni model za predviđanje individualne doze acenokumarola može pokazati prednosti u odnosu na modele koji se koriste na generalizovan način. Takođe, VKORC1 varijante koje izazivaju rezistenciju na kumarin treba uzeti u obzir prilikom planiranja terapije.
AB  - Introduction/Objective Coumarin therapy represents one of the best models for applying pharmacogenetics. The contribution of factors influencing coumarin therapy can vary significantly between ethnic groups, which justifies conducting population-specific studies. The aim of this study was to analyze the influence of the most important genetic factors (VKORC1 and CYP2C9 genes) that affect coumarin therapy in patients from Serbia. Methods A retrospective study involving 207 patients on acenocoumarol therapy was conducted. Genetic analyses were performed by direct sequencing. Influence on acenocoumarol dose of variants (VKORC1, CYP2C9*2, CYP2C9*3) causing hypersensitivity and VKORC1 variants causing resistance to acenocoumarol were analyzed. Multiple regression analysis was used to design a mathematical model for predicting individual drug dosage based on clinical-demographic and genetic data. Results The study confirmed significant influence of the analyzed genetic factors on acenocoumarol maintenance dose. We designed mathematical model for predicting individual acenocoumarol dose and its unadjusted R2 was 61.8. In the testing cohort, our model gave R2 value of 42.6 and showed better prediction in comparison with model given by other authors. In the analyzed patients, nine different variants in the VKORC1 coding region were found. Among carriers of these variants 78% were completely resistant, and it was not possible to achieve therapeutic effect even with high doses of acenocoumarol. Conclusions Population-specific model for prediction individual dose of acenocoumarol, may show advantages over protocols that are used in a generalized manner. Also, VKORC1 variants which cause coumarin resistance should be considered when planning therapy.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije
T1  - The 'VKORC1' and 'CYP2C9' gene variants as pharmacogenetic factors in acenocoumarol therapy in Serbian patients: Consideration of hypersensitivity and resistance
EP  - 162
IS  - 3-4
SP  - 156
VL  - 150
DO  - 10.2298/SARH211118013R
ER  - 

@article{
author = "Rakićević, Ljiljana and Kovač, Mirjana and Radojković, Dragica and Radojković, Milica",
year = "2022",
abstract = "Uvod/Cilj Terapija kumarinima predstavlja jedan od najboljih modela za primenu farmakogenetike. Doprinos faktora koji utiču na terapiju kumarinima može značajno da varira između etničkih grupa, što opravdava sprovođenje studija specifičnih za populaciju. Cilj ove studije je bio da se analizira uticaj najvažnijih genetičkih faktora (geni VKORC1 i CYP2C9) koji utiču na terapiju kumarinima kod bolesnika iz Srbije. Metode Sprovedena je retrospektivna studija koja je obuhvatila 207 bolesnika na terapiji acenokumarolom. Genetičke analize su vršene direktnim sekvenciranjem. Analiziran je uticaj na dozu acenokumarola varijanti (VKORC1*2, CYP2C9*2, CYP2C9*3) koje izazivaju preosetljivost i varijanti gena VKORC1 koje izazivaju rezistenciju na kumarine. Višestruka regresiona analiza je korišćena u cilju dizajniranja matematičkog modela za predviđanje individualne doze leka na osnovu kliničko-demografskih i genetičkih podataka. Rezultati Studija je potvrdila značajan uticaj analiziranih genetičkih faktora na održavanje doze acenokumarola. Dizajniran je matematički model za predviđanje individualne doze acenokumarola i njegov nekorigovani R2 je bio 61,8. Prilikom testiranja, naš model je dao R2 vrednost od 42,6 i pokazao bolje predviđanje u poređenju sa modelom koji su dali drugi autori. Kod analiziranih bolesnika pronađeno je devet različitih varijanti u kodirajućem regionu gena VKORC1. Među nosiocima ovih varijanti 78% je bilo potpuno rezistentno, te nije bilo moguće postići terapeutski efekat čak ni sa visokim dozama acenokumarola. Zaključci Populacioni model za predviđanje individualne doze acenokumarola može pokazati prednosti u odnosu na modele koji se koriste na generalizovan način. Takođe, VKORC1 varijante koje izazivaju rezistenciju na kumarin treba uzeti u obzir prilikom planiranja terapije., Introduction/Objective Coumarin therapy represents one of the best models for applying pharmacogenetics. The contribution of factors influencing coumarin therapy can vary significantly between ethnic groups, which justifies conducting population-specific studies. The aim of this study was to analyze the influence of the most important genetic factors (VKORC1 and CYP2C9 genes) that affect coumarin therapy in patients from Serbia. Methods A retrospective study involving 207 patients on acenocoumarol therapy was conducted. Genetic analyses were performed by direct sequencing. Influence on acenocoumarol dose of variants (VKORC1, CYP2C9*2, CYP2C9*3) causing hypersensitivity and VKORC1 variants causing resistance to acenocoumarol were analyzed. Multiple regression analysis was used to design a mathematical model for predicting individual drug dosage based on clinical-demographic and genetic data. Results The study confirmed significant influence of the analyzed genetic factors on acenocoumarol maintenance dose. We designed mathematical model for predicting individual acenocoumarol dose and its unadjusted R2 was 61.8. In the testing cohort, our model gave R2 value of 42.6 and showed better prediction in comparison with model given by other authors. In the analyzed patients, nine different variants in the VKORC1 coding region were found. Among carriers of these variants 78% were completely resistant, and it was not possible to achieve therapeutic effect even with high doses of acenocoumarol. Conclusions Population-specific model for prediction individual dose of acenocoumarol, may show advantages over protocols that are used in a generalized manner. Also, VKORC1 variants which cause coumarin resistance should be considered when planning therapy.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije, The 'VKORC1' and 'CYP2C9' gene variants as pharmacogenetic factors in acenocoumarol therapy in Serbian patients: Consideration of hypersensitivity and resistance",
pages = "162-156",
number = "3-4",
volume = "150",
doi = "10.2298/SARH211118013R"
}

Rakićević, L., Kovač, M., Radojković, D.,& Radojković, M.. (2022). Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 150(3-4), 156-162.
https://doi.org/10.2298/SARH211118013R

Rakićević L, Kovač M, Radojković D, Radojković M. Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije. in Srpski arhiv za celokupno lekarstvo. 2022;150(3-4):156-162.
doi:10.2298/SARH211118013R .

Rakićević, Ljiljana, Kovač, Mirjana, Radojković, Dragica, Radojković, Milica, "Varijante gena "VKORC1" i "CYP2C9" kao farmakogenetički faktori u terapiji acenokumarolom kod bolesnika u Srbiji - razmatranje preosetljivosti i rezistencije" in Srpski arhiv za celokupno lekarstvo, 150, no. 3-4 (2022):156-162,
https://doi.org/10.2298/SARH211118013R . .

TY  - JOUR
AU  - Andjelic, Jelic M.
AU  - Radojković, Dragica
AU  - Nikolić, Aleksandra
AU  - Rakićević, Ljiljana
AU  - Babić, Tamara
AU  - Jelic, D.
AU  - Lalic, N. M.
PY  - 2022
UR  - https://sciendo.com/article/10.2478/bjmg-2022-0001
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1787
AB  - AbstractVascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to
PB  - Sciendo
T2  - Balkan Journal of Medical Genetics
T2  - Balkan Journal of Medical Genetics
T1  - Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients
EP  - 40
IS  - 1
SP  - 35
VL  - 25
DO  - 10.2478/bjmg-2022-0001
ER  - 

@article{
author = "Andjelic, Jelic M. and Radojković, Dragica and Nikolić, Aleksandra and Rakićević, Ljiljana and Babić, Tamara and Jelic, D. and Lalic, N. M.",
year = "2022",
abstract = "AbstractVascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to",
publisher = "Sciendo",
journal = "Balkan Journal of Medical Genetics, Balkan Journal of Medical Genetics",
title = "Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients",
pages = "40-35",
number = "1",
volume = "25",
doi = "10.2478/bjmg-2022-0001"
}

Andjelic, J. M., Radojković, D., Nikolić, A., Rakićević, L., Babić, T., Jelic, D.,& Lalic, N. M.. (2022). Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients. in Balkan Journal of Medical Genetics
Sciendo., 25(1), 35-40.
https://doi.org/10.2478/bjmg-2022-0001

Andjelic JM, Radojković D, Nikolić A, Rakićević L, Babić T, Jelic D, Lalic NM. Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients. in Balkan Journal of Medical Genetics. 2022;25(1):35-40.
doi:10.2478/bjmg-2022-0001 .

Andjelic, Jelic M., Radojković, Dragica, Nikolić, Aleksandra, Rakićević, Ljiljana, Babić, Tamara, Jelic, D., Lalic, N. M., "Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients" in Balkan Journal of Medical Genetics, 25, no. 1 (2022):35-40,
https://doi.org/10.2478/bjmg-2022-0001 . .

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 . .

TY  - JOUR
AU  - Nikolić, Aleksandra
AU  - Despotović, Jovana
AU  - Babić, Tamara
AU  - Antić, Jadranka
AU  - Marković, Srdjan
AU  - Krivokapić, Zoran
AU  - Radojković, Dragica
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1595
AB  - In colorectal cancer (CRC), inactivation of SMAD4 occurs early in the disease development and SMAD4 represents one of key driver genes in progression and metastasis. Loss of SMAD4 protein expression is a relatively common feature of sporadic colorectal cancers, and it was observed to be even more frequent in tumors of patients with early onset disease and also more frequent in microsatellite stable tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain in colorectal cancer patients with early onset disease and microsatellite stable tumors. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients. The study was conducted in a selected set of DNA samples extracted from the tumors of CRC patients who had less than 50 years at the time of diagnosis. Genetic analysis of C-terminal domain has encompassed analysis of exons 9, 10, 11 and 12 of the SMAD4 gene by PCR and direct DNA sequencing. Among the twenty analyzed tumor DNAs, one sample was found to harbor a SMAD4 variant: NC_000018.9:g.48591918C  gt  T; (NM005359.5: c.1081C  gt  T; Arg361Cys). The variant was discovered in exon 9, affecting the codon 361, which represents a mutational hot spot within the SMAD4 gene. This variant was discovered in homozygous state in the tumor of a 47 yr old female with T3 stage carcinoma of the right colon. Considering the incidence and functional consequences of SMAD4 exon 9 variants, the screening of this region could be a useful low cost strategy for the genetic analysis of colorectal tumors from patients with early onset disease, as well as for susceptibility testing.
PB  - Pleiades Publishing Inc, New York
T2  - Cytology and Genetics
T1  - SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study
EP  - 276
IS  - 3
SP  - 273
VL  - 56
DO  - 10.3103/S0095452722030082
ER  - 

@article{
author = "Nikolić, Aleksandra and Despotović, Jovana and Babić, Tamara and Antić, Jadranka and Marković, Srdjan and Krivokapić, Zoran and Radojković, Dragica",
year = "2022",
abstract = "In colorectal cancer (CRC), inactivation of SMAD4 occurs early in the disease development and SMAD4 represents one of key driver genes in progression and metastasis. Loss of SMAD4 protein expression is a relatively common feature of sporadic colorectal cancers, and it was observed to be even more frequent in tumors of patients with early onset disease and also more frequent in microsatellite stable tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain in colorectal cancer patients with early onset disease and microsatellite stable tumors. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients. The study was conducted in a selected set of DNA samples extracted from the tumors of CRC patients who had less than 50 years at the time of diagnosis. Genetic analysis of C-terminal domain has encompassed analysis of exons 9, 10, 11 and 12 of the SMAD4 gene by PCR and direct DNA sequencing. Among the twenty analyzed tumor DNAs, one sample was found to harbor a SMAD4 variant: NC_000018.9:g.48591918C  gt  T; (NM005359.5: c.1081C  gt  T; Arg361Cys). The variant was discovered in exon 9, affecting the codon 361, which represents a mutational hot spot within the SMAD4 gene. This variant was discovered in homozygous state in the tumor of a 47 yr old female with T3 stage carcinoma of the right colon. Considering the incidence and functional consequences of SMAD4 exon 9 variants, the screening of this region could be a useful low cost strategy for the genetic analysis of colorectal tumors from patients with early onset disease, as well as for susceptibility testing.",
publisher = "Pleiades Publishing Inc, New York",
journal = "Cytology and Genetics",
title = "SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study",
pages = "276-273",
number = "3",
volume = "56",
doi = "10.3103/S0095452722030082"
}

Nikolić, A., Despotović, J., Babić, T., Antić, J., Marković, S., Krivokapić, Z.,& Radojković, D.. (2022). SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study. in Cytology and Genetics
Pleiades Publishing Inc, New York., 56(3), 273-276.
https://doi.org/10.3103/S0095452722030082

Nikolić A, Despotović J, Babić T, Antić J, Marković S, Krivokapić Z, Radojković D. SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study. in Cytology and Genetics. 2022;56(3):273-276.
doi:10.3103/S0095452722030082 .

Nikolić, Aleksandra, Despotović, Jovana, Babić, Tamara, Antić, Jadranka, Marković, Srdjan, Krivokapić, Zoran, Radojković, Dragica, "SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study" in Cytology and Genetics, 56, no. 3 (2022):273-276,
https://doi.org/10.3103/S0095452722030082 . .

TY  - CONF
AU  - Bačković, Dragana
AU  - Novković, Mirjana
AU  - Matić, Dragan
AU  - Antonijević, Nebojša
AU  - Strugarević, Evgenija
AU  - Kovač, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Rakićević, Ljiljana
AU  - Radojković, Dragica
PY  - 2021
UR  - https://www.uksrb.rs/en/magazine/archive/heart-and-blood-vessels-number-32021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2344
AB  - Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.
PB  - Beograd : Udruženje kardiologa Srbije
C3  - Heart and Blood Vessels
T1  - Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy
IS  - 3
VL  - 40
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2344
ER  - 

@conference{
author = "Bačković, Dragana and Novković, Mirjana and Matić, Dragan and Antonijević, Nebojša and Strugarević, Evgenija and Kovač, Mirjana and Kušić-Tišma, Jelena and Rakićević, Ljiljana and Radojković, Dragica",
year = "2021",
abstract = "Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.",
publisher = "Beograd : Udruženje kardiologa Srbije",
journal = "Heart and Blood Vessels",
title = "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy",
number = "3",
volume = "40",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2344"
}

Bačković, D., Novković, M., Matić, D., Antonijević, N., Strugarević, E., Kovač, M., Kušić-Tišma, J., Rakićević, L.,& Radojković, D.. (2021). Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels
Beograd : Udruženje kardiologa Srbije., 40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344

Bačković D, Novković M, Matić D, Antonijević N, Strugarević E, Kovač M, Kušić-Tišma J, Rakićević L, Radojković D. Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels. 2021;40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344 .

Bačković, Dragana, Novković, Mirjana, Matić, Dragan, Antonijević, Nebojša, Strugarević, Evgenija, Kovač, Mirjana, Kušić-Tišma, Jelena, Rakićević, Ljiljana, Radojković, Dragica, "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy" in Heart and Blood Vessels, 40, no. 3 (2021),
https://hdl.handle.net/21.15107/rcub_imagine_2344 .

TY  - JOUR
AU  - Prosenc-Zmrzljak, Ursula
AU  - Kosir, Rok
AU  - Krivokapić, Zoran
AU  - Radojković, Dragica
AU  - Nikolić, Aleksandra
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1494
AB  - Liquid biopsy and cell-free DNA (cfDNA) show great promise in cancer diagnostics. In this study, we designed a custom droplet digital PCR (ddPCR) assay for the quantification and quality control of cfDNA isolated from serum. The assay was validated on a group of locally advanced colorectal cancer (CRC) patients and two control groups-patients with hemorrhoids and healthy individuals. The assay shows a high correlation with Qubit measurement (r = 0.976) but offers a higher dynamic range. Mean concentrations of cfDNA were 12.36 ng/mu L, 5.17 ng/mu L, and 0.29 ng/mu L for CRC, hemorrhoid patients, and healthy controls, respectively. The quality of cfDNA was assessed with the measurement of B-cell DNA contamination. On a subset of CRC patients, we compared the mutation status on KRAS (G12A, G12D, G12V, G13D) and BRAF (V600E) genes in the primary tumor and cfDNA isolated from the serum. A total of 70.6% of primary tumor samples were mutated, and the mean fractional abundance of mutations was 9.50%. The matching serum samples were mutated in 38% cases with an average fractional abundance of 0.23%. We conclude that any decisions based solely on the amount of cfDNA present in patient serum must be interpreted carefully and in the context of co-morbidities. This study explores the potential of ddPCR somatic mutations detection from liquid biopsy as a supplement to tissue biopsy in targeted personalized CRC patient management.
PB  - MDPI, Basel
T2  - Genes
T1  - Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients
IS  - 2
VL  - 12
DO  - 10.3390/genes12020289
ER  - 

@article{
author = "Prosenc-Zmrzljak, Ursula and Kosir, Rok and Krivokapić, Zoran and Radojković, Dragica and Nikolić, Aleksandra",
year = "2021",
abstract = "Liquid biopsy and cell-free DNA (cfDNA) show great promise in cancer diagnostics. In this study, we designed a custom droplet digital PCR (ddPCR) assay for the quantification and quality control of cfDNA isolated from serum. The assay was validated on a group of locally advanced colorectal cancer (CRC) patients and two control groups-patients with hemorrhoids and healthy individuals. The assay shows a high correlation with Qubit measurement (r = 0.976) but offers a higher dynamic range. Mean concentrations of cfDNA were 12.36 ng/mu L, 5.17 ng/mu L, and 0.29 ng/mu L for CRC, hemorrhoid patients, and healthy controls, respectively. The quality of cfDNA was assessed with the measurement of B-cell DNA contamination. On a subset of CRC patients, we compared the mutation status on KRAS (G12A, G12D, G12V, G13D) and BRAF (V600E) genes in the primary tumor and cfDNA isolated from the serum. A total of 70.6% of primary tumor samples were mutated, and the mean fractional abundance of mutations was 9.50%. The matching serum samples were mutated in 38% cases with an average fractional abundance of 0.23%. We conclude that any decisions based solely on the amount of cfDNA present in patient serum must be interpreted carefully and in the context of co-morbidities. This study explores the potential of ddPCR somatic mutations detection from liquid biopsy as a supplement to tissue biopsy in targeted personalized CRC patient management.",
publisher = "MDPI, Basel",
journal = "Genes",
title = "Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients",
number = "2",
volume = "12",
doi = "10.3390/genes12020289"
}

Prosenc-Zmrzljak, U., Kosir, R., Krivokapić, Z., Radojković, D.,& Nikolić, A.. (2021). Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients. in Genes
MDPI, Basel., 12(2).
https://doi.org/10.3390/genes12020289

Prosenc-Zmrzljak U, Kosir R, Krivokapić Z, Radojković D, Nikolić A. Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients. in Genes. 2021;12(2).
doi:10.3390/genes12020289 .

Prosenc-Zmrzljak, Ursula, Kosir, Rok, Krivokapić, Zoran, Radojković, Dragica, Nikolić, Aleksandra, "Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients" in Genes, 12, no. 2 (2021),
https://doi.org/10.3390/genes12020289 . .

TY  - JOUR
AU  - Bošković, Srđan
AU  - Juez, Ruben Marin
AU  - Stamenković, Nemanja
AU  - Radojković, Dragica
AU  - Stainier, Didier Y. R.
AU  - Kojić, Snežana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1425
AB  - Ankyrin repeat domain 1 (ANKRD1) is a functionally pleiotropic protein found in the nuclei and sarcomeres of cardiac and skeletal muscles, with a proposed role in linking myofibrilar stress and transcriptional regulation. Rapid upregulation of its expression in response to both physiological and pathological stress supports the involvement of ANKRD1 in muscle tissue adaptation and remodeling. However, the exact role of ANKRD1 remains poorly understood. To begin to investigate its function at higher resolution, we have generated and characterized a TgBAC(ankrd1a:EGFP) zebrafish line. This reporter line displays transgene expression in slow skeletal muscle fibers during development and exercise responsiveness in adult cardiac muscle. To better understand the role of Ankrd1a in pathological conditions in adult zebrafish, we assessed ankrd1a expression after cardiac ventricle cryoinjury and observed localized upregulation in cardiomyocytes in the border zone. We show that this expression in injured hearts is recapitulated by the TgBAC(ankrd1a:EGFP) reporter. Our results identify novel expression domains of ankrd1a and suggest an important role for Ankrd1a in the early stress response and regeneration of cardiac tissue. This new reporter line will help decipher the role of Ankrd1a in striated muscle stress response, including after cardiac injury.
PB  - Elsevier, Amsterdam
T2  - Gene
T1  - The stress responsive gene ankrd1a is dynamically regulated during skeletal muscle development and upregulated following cardiac injury in border zone cardiomyocytes in adult zebrafish
VL  - 792
DO  - 10.1016/j.gene.2021.145725
ER  - 

@article{
author = "Bošković, Srđan and Juez, Ruben Marin and Stamenković, Nemanja and Radojković, Dragica and Stainier, Didier Y. R. and Kojić, Snežana",
year = "2021",
abstract = "Ankyrin repeat domain 1 (ANKRD1) is a functionally pleiotropic protein found in the nuclei and sarcomeres of cardiac and skeletal muscles, with a proposed role in linking myofibrilar stress and transcriptional regulation. Rapid upregulation of its expression in response to both physiological and pathological stress supports the involvement of ANKRD1 in muscle tissue adaptation and remodeling. However, the exact role of ANKRD1 remains poorly understood. To begin to investigate its function at higher resolution, we have generated and characterized a TgBAC(ankrd1a:EGFP) zebrafish line. This reporter line displays transgene expression in slow skeletal muscle fibers during development and exercise responsiveness in adult cardiac muscle. To better understand the role of Ankrd1a in pathological conditions in adult zebrafish, we assessed ankrd1a expression after cardiac ventricle cryoinjury and observed localized upregulation in cardiomyocytes in the border zone. We show that this expression in injured hearts is recapitulated by the TgBAC(ankrd1a:EGFP) reporter. Our results identify novel expression domains of ankrd1a and suggest an important role for Ankrd1a in the early stress response and regeneration of cardiac tissue. This new reporter line will help decipher the role of Ankrd1a in striated muscle stress response, including after cardiac injury.",
publisher = "Elsevier, Amsterdam",
journal = "Gene",
title = "The stress responsive gene ankrd1a is dynamically regulated during skeletal muscle development and upregulated following cardiac injury in border zone cardiomyocytes in adult zebrafish",
volume = "792",
doi = "10.1016/j.gene.2021.145725"
}

Bošković, S., Juez, R. M., Stamenković, N., Radojković, D., Stainier, D. Y. R.,& Kojić, S.. (2021). The stress responsive gene ankrd1a is dynamically regulated during skeletal muscle development and upregulated following cardiac injury in border zone cardiomyocytes in adult zebrafish. in Gene
Elsevier, Amsterdam., 792.
https://doi.org/10.1016/j.gene.2021.145725

Bošković S, Juez RM, Stamenković N, Radojković D, Stainier DYR, Kojić S. The stress responsive gene ankrd1a is dynamically regulated during skeletal muscle development and upregulated following cardiac injury in border zone cardiomyocytes in adult zebrafish. in Gene. 2021;792.
doi:10.1016/j.gene.2021.145725 .

Bošković, Srđan, Juez, Ruben Marin, Stamenković, Nemanja, Radojković, Dragica, Stainier, Didier Y. R., Kojić, Snežana, "The stress responsive gene ankrd1a is dynamically regulated during skeletal muscle development and upregulated following cardiac injury in border zone cardiomyocytes in adult zebrafish" in Gene, 792 (2021),
https://doi.org/10.1016/j.gene.2021.145725 . .

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 . .

TY  - JOUR
AU  - Stamenković, Nemanja
AU  - Jasnić, Jovana
AU  - Novković, Mirjana
AU  - Milošević, Emilija
AU  - Bošković, Srđan
AU  - Kojić, Ana
AU  - Popić, Kristina
AU  - Stanković, Marija
AU  - Wang, Yajun
AU  - Milenković, Sanja
AU  - Radojković, Dragica
AU  - Ma, Guada
AU  - Kojić, Snežana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1307
AB  - Striated muscle signaling protein and transcriptional regulator ANKRD2 participates in myogenesis, myogenic differentiation, muscle adaptation and stress response. It is preferentially expressed in slow, oxidative fibers of mammalian skeletal muscle. In this study, we report on characterization of chickenANKRD2. The chickenANKRD2coding region contains 1002 bp and encodes a 334-amino acid protein which shares approximately 58% identity with human and mouse orthologs, mostly in the conserved region of ankyrin repeats. Comprehensive analysis of theANKRD2gene and protein expression in adult chicken demonstrated its predominant expression in red muscles of thigh and drumstick, compared to white muscle. It was not detected in heart and white pectoral muscle. Uneven expression of ANKRD2 in chicken skeletal muscles, observed by immunohistochemistry, was attributed to its selective expression in slow, oxidative, type I and fast, oxidative-glycolytic, type IIA myofibers. Association of chickenANKRD2with phenotypic differences between red and white muscles points to its potential role in the process of myofiber-type specification. In addition to expression in slow oxidative myofibers, as demonstrated for mammalian protein, chicken ANKRD2 was also detected in fast fibers with mixed oxidative and glycolytic metabolism. This finding suggests thatANKRD2is responsive to metabolic differences between types of avian myofibers and orientates future studies towards investigation of its role in molecular mechanisms of myofiber-type-specific gene expression.
PB  - Springer, New York
T2  - Histochemistry and Cell Biology
T1  - Cloning and expression profiling of muscle regulator ANKRD2 in domestic chickenGallus gallus
EP  - 396
IS  - 4
SP  - 383
VL  - 154
DO  - 10.1007/s00418-020-01899-1
ER  - 

@article{
author = "Stamenković, Nemanja and Jasnić, Jovana and Novković, Mirjana and Milošević, Emilija and Bošković, Srđan and Kojić, Ana and Popić, Kristina and Stanković, Marija and Wang, Yajun and Milenković, Sanja and Radojković, Dragica and Ma, Guada and Kojić, Snežana",
year = "2020",
abstract = "Striated muscle signaling protein and transcriptional regulator ANKRD2 participates in myogenesis, myogenic differentiation, muscle adaptation and stress response. It is preferentially expressed in slow, oxidative fibers of mammalian skeletal muscle. In this study, we report on characterization of chickenANKRD2. The chickenANKRD2coding region contains 1002 bp and encodes a 334-amino acid protein which shares approximately 58% identity with human and mouse orthologs, mostly in the conserved region of ankyrin repeats. Comprehensive analysis of theANKRD2gene and protein expression in adult chicken demonstrated its predominant expression in red muscles of thigh and drumstick, compared to white muscle. It was not detected in heart and white pectoral muscle. Uneven expression of ANKRD2 in chicken skeletal muscles, observed by immunohistochemistry, was attributed to its selective expression in slow, oxidative, type I and fast, oxidative-glycolytic, type IIA myofibers. Association of chickenANKRD2with phenotypic differences between red and white muscles points to its potential role in the process of myofiber-type specification. In addition to expression in slow oxidative myofibers, as demonstrated for mammalian protein, chicken ANKRD2 was also detected in fast fibers with mixed oxidative and glycolytic metabolism. This finding suggests thatANKRD2is responsive to metabolic differences between types of avian myofibers and orientates future studies towards investigation of its role in molecular mechanisms of myofiber-type-specific gene expression.",
publisher = "Springer, New York",
journal = "Histochemistry and Cell Biology",
title = "Cloning and expression profiling of muscle regulator ANKRD2 in domestic chickenGallus gallus",
pages = "396-383",
number = "4",
volume = "154",
doi = "10.1007/s00418-020-01899-1"
}

Stamenković, N., Jasnić, J., Novković, M., Milošević, E., Bošković, S., Kojić, A., Popić, K., Stanković, M., Wang, Y., Milenković, S., Radojković, D., Ma, G.,& Kojić, S.. (2020). Cloning and expression profiling of muscle regulator ANKRD2 in domestic chickenGallus gallus. in Histochemistry and Cell Biology
Springer, New York., 154(4), 383-396.
https://doi.org/10.1007/s00418-020-01899-1

Stamenković N, Jasnić J, Novković M, Milošević E, Bošković S, Kojić A, Popić K, Stanković M, Wang Y, Milenković S, Radojković D, Ma G, Kojić S. Cloning and expression profiling of muscle regulator ANKRD2 in domestic chickenGallus gallus. in Histochemistry and Cell Biology. 2020;154(4):383-396.
doi:10.1007/s00418-020-01899-1 .

Stamenković, Nemanja, Jasnić, Jovana, Novković, Mirjana, Milošević, Emilija, Bošković, Srđan, Kojić, Ana, Popić, Kristina, Stanković, Marija, Wang, Yajun, Milenković, Sanja, Radojković, Dragica, Ma, Guada, Kojić, Snežana, "Cloning and expression profiling of muscle regulator ANKRD2 in domestic chickenGallus gallus" in Histochemistry and Cell Biology, 154, no. 4 (2020):383-396,
https://doi.org/10.1007/s00418-020-01899-1 . .

TY  - JOUR
AU  - Divac Rankov, Aleksandra
AU  - Kušić-Tišma, Jelena
AU  - Ljujić, Mila
AU  - Nikolić, Aleksandra
AU  - Milosević, Katarina
AU  - Dautović, Gordana Vilotijevic
AU  - Radojković, Dragica
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1381
AB  - Background: High heterogeneity levels of cystic fibrosis transmembrane regulator (CFTR) are manifested in different populations. The aim of this study was to analyze comprehensively all mutations in the CFTR gene in Serbian patients with cystic fibrosis (CF) and to use the findings to propose a testing algorithm for the Serbian population. Materials and Methods: Cascade screening was employed to detect mutations in the CFTR gene of 90 patients suspected of having CF, using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism or PCR-mediated site directed mutagenesis, Sanger sequencing, and/or next-generation sequencing. Results: This is the first report for the Serbian CF population where single nucleotide polymorphisms, small insertions and deletions, large genome rearrangements, and copy number variants were analyzed in detail. A high degree of heterogeneity within the CFTR was documented among our cohort of 90 patients. We identified 19 CF-causing mutations and 3 with varying consequences, including a previously unreported deletion of the entire exon 11. Conclusion: Considering the spectrum and frequency of mutations found, we recommend a multistep sequencing algorithm in combination with evaluation of large rearrangements for future analyses of the CFTR gene in the Serbian population.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Genetic Testing and Molecular Biomarkers
T1  - Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges
EP  - 216
IS  - 4
SP  - 212
VL  - 24
DO  - 10.1089/gtmb.2019.0171
ER  - 

@article{
author = "Divac Rankov, Aleksandra and Kušić-Tišma, Jelena and Ljujić, Mila and Nikolić, Aleksandra and Milosević, Katarina and Dautović, Gordana Vilotijevic and Radojković, Dragica",
year = "2020",
abstract = "Background: High heterogeneity levels of cystic fibrosis transmembrane regulator (CFTR) are manifested in different populations. The aim of this study was to analyze comprehensively all mutations in the CFTR gene in Serbian patients with cystic fibrosis (CF) and to use the findings to propose a testing algorithm for the Serbian population. Materials and Methods: Cascade screening was employed to detect mutations in the CFTR gene of 90 patients suspected of having CF, using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism or PCR-mediated site directed mutagenesis, Sanger sequencing, and/or next-generation sequencing. Results: This is the first report for the Serbian CF population where single nucleotide polymorphisms, small insertions and deletions, large genome rearrangements, and copy number variants were analyzed in detail. A high degree of heterogeneity within the CFTR was documented among our cohort of 90 patients. We identified 19 CF-causing mutations and 3 with varying consequences, including a previously unreported deletion of the entire exon 11. Conclusion: Considering the spectrum and frequency of mutations found, we recommend a multistep sequencing algorithm in combination with evaluation of large rearrangements for future analyses of the CFTR gene in the Serbian population.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Genetic Testing and Molecular Biomarkers",
title = "Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges",
pages = "216-212",
number = "4",
volume = "24",
doi = "10.1089/gtmb.2019.0171"
}

Divac Rankov, A., Kušić-Tišma, J., Ljujić, M., Nikolić, A., Milosević, K., Dautović, G. V.,& Radojković, D.. (2020). Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges. in Genetic Testing and Molecular Biomarkers
Mary Ann Liebert, Inc, New Rochelle., 24(4), 212-216.
https://doi.org/10.1089/gtmb.2019.0171

Divac Rankov A, Kušić-Tišma J, Ljujić M, Nikolić A, Milosević K, Dautović GV, Radojković D. Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges. in Genetic Testing and Molecular Biomarkers. 2020;24(4):212-216.
doi:10.1089/gtmb.2019.0171 .

Divac Rankov, Aleksandra, Kušić-Tišma, Jelena, Ljujić, Mila, Nikolić, Aleksandra, Milosević, Katarina, Dautović, Gordana Vilotijevic, Radojković, Dragica, "Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges" in Genetic Testing and Molecular Biomarkers, 24, no. 4 (2020):212-216,
https://doi.org/10.1089/gtmb.2019.0171 . .

TY  - JOUR
AU  - Dragičević, Sandra
AU  - Kovacević, Draginja
AU  - Divac Rankov, Aleksandra
AU  - Nikolić, Aleksandra
AU  - Radojković, Dragica
AU  - Radović, Svetlana
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1233
AB  - Tussilago farfara (coltsfoot) and Verbascum thapsus (mullein) have been used as folk remedies for treating respiratory disorders. The aim of this study was to test the toxicity of the water extracts of T. farfara and V. thapsus in vivo in zebrafish and in vitro in BEAS 2B epithelial bronchial cells. To the best of our knowledge, this is the first study to investigate the antioxidative properties of T. farfara and V. thapsus extracts in cell culture. Our results show that the T. farfara leaf extract does not produce toxic effects on zebrafish embryos or BEAS 2B cells, and that it has a protective effect in BEAS 2B after induction of oxidative stress. The water extract from V. thapsus displayed pronounced toxic effects on zebrafish embryos and BEAS 2B cells and did not exhibit a significant antioxidative effect on BEAS 2B cells exposed to oxidative stress. Our results suggest that the use of T. farfara water leaf extract is potentially safe and effective in treating respiratory disorders, whereas the use of V. thapsus needs further investigation.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells
EP  - 416
IS  - 3
SP  - 409
VL  - 71
DO  - 10.2298/ABS181213022D
ER  - 

@article{
author = "Dragičević, Sandra and Kovacević, Draginja and Divac Rankov, Aleksandra and Nikolić, Aleksandra and Radojković, Dragica and Radović, Svetlana",
year = "2019",
abstract = "Tussilago farfara (coltsfoot) and Verbascum thapsus (mullein) have been used as folk remedies for treating respiratory disorders. The aim of this study was to test the toxicity of the water extracts of T. farfara and V. thapsus in vivo in zebrafish and in vitro in BEAS 2B epithelial bronchial cells. To the best of our knowledge, this is the first study to investigate the antioxidative properties of T. farfara and V. thapsus extracts in cell culture. Our results show that the T. farfara leaf extract does not produce toxic effects on zebrafish embryos or BEAS 2B cells, and that it has a protective effect in BEAS 2B after induction of oxidative stress. The water extract from V. thapsus displayed pronounced toxic effects on zebrafish embryos and BEAS 2B cells and did not exhibit a significant antioxidative effect on BEAS 2B cells exposed to oxidative stress. Our results suggest that the use of T. farfara water leaf extract is potentially safe and effective in treating respiratory disorders, whereas the use of V. thapsus needs further investigation.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells",
pages = "416-409",
number = "3",
volume = "71",
doi = "10.2298/ABS181213022D"
}

Dragičević, S., Kovacević, D., Divac Rankov, A., Nikolić, A., Radojković, D.,& Radović, S.. (2019). Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 71(3), 409-416.
https://doi.org/10.2298/ABS181213022D

Dragičević S, Kovacević D, Divac Rankov A, Nikolić A, Radojković D, Radović S. Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells. in Archives of Biological Sciences. 2019;71(3):409-416.
doi:10.2298/ABS181213022D .

Dragičević, Sandra, Kovacević, Draginja, Divac Rankov, Aleksandra, Nikolić, Aleksandra, Radojković, Dragica, Radović, Svetlana, "Evaluation of toxicity and antioxidative effects of Tussilago farfara and Verbascum thapsus water extracts in zebrafish and in bronchial epithelial cells" in Archives of Biological Sciences, 71, no. 3 (2019):409-416,
https://doi.org/10.2298/ABS181213022D . .

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  - 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 . .

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 . .

TY  - JOUR
AU  - Jeremić, Ivica
AU  - Đurić, Olivera
AU  - Nikolić, Milos
AU  - Vlajnić, Marina
AU  - Nikolić, Aleksandra
AU  - Radojković, Dragica
AU  - Bonaci-Nikolić, Branka
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1257
AB  - Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naive SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p  lt  0.001), BAFF and DNase I concentration (p  lt  0.01). Contrary, NETolytic activity was lower in SLE patients (p  lt  0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p  lt  0.001, p  lt  0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p  lt  0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p  lt  0.01), cfDNA and BAFF levels (p  lt  0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p  lt  0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naive SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression.
PB  - Springer Heidelberg, Heidelberg
T2  - Rheumatology International
T1  - Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus
EP  - 1857
IS  - 11
SP  - 1849
VL  - 39
DO  - 10.1007/s00296-019-04426-1
ER  - 

@article{
author = "Jeremić, Ivica and Đurić, Olivera and Nikolić, Milos and Vlajnić, Marina and Nikolić, Aleksandra and Radojković, Dragica and Bonaci-Nikolić, Branka",
year = "2019",
abstract = "Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naive SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p  lt  0.001), BAFF and DNase I concentration (p  lt  0.01). Contrary, NETolytic activity was lower in SLE patients (p  lt  0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p  lt  0.001, p  lt  0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p  lt  0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p  lt  0.01), cfDNA and BAFF levels (p  lt  0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p  lt  0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naive SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Rheumatology International",
title = "Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus",
pages = "1857-1849",
number = "11",
volume = "39",
doi = "10.1007/s00296-019-04426-1"
}

Jeremić, I., Đurić, O., Nikolić, M., Vlajnić, M., Nikolić, A., Radojković, D.,& Bonaci-Nikolić, B.. (2019). Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus. in Rheumatology International
Springer Heidelberg, Heidelberg., 39(11), 1849-1857.
https://doi.org/10.1007/s00296-019-04426-1

Jeremić I, Đurić O, Nikolić M, Vlajnić M, Nikolić A, Radojković D, Bonaci-Nikolić B. Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus. in Rheumatology International. 2019;39(11):1849-1857.
doi:10.1007/s00296-019-04426-1 .

Jeremić, Ivica, Đurić, Olivera, Nikolić, Milos, Vlajnić, Marina, Nikolić, Aleksandra, Radojković, Dragica, Bonaci-Nikolić, Branka, "Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus" in Rheumatology International, 39, no. 11 (2019):1849-1857,
https://doi.org/10.1007/s00296-019-04426-1 . .

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 . .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Kovac, Zeljko
AU  - Tomasević, Zorica
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Radojković, Dragica
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1250
PB  - Wiley, Hoboken
T2  - Breast Journal
T1  - Breast cancer and recurrent thrombosis - Results from prospective single center study
EP  - 785
IS  - 4
SP  - 783
VL  - 25
DO  - 10.1111/tbj.13326
ER  - 

@article{
author = "Kovač, Mirjana and Kovac, Zeljko and Tomasević, Zorica and Tomić, Branko and Gvozdenov, Maja and Radojković, Dragica",
year = "2019",
publisher = "Wiley, Hoboken",
journal = "Breast Journal",
title = "Breast cancer and recurrent thrombosis - Results from prospective single center study",
pages = "785-783",
number = "4",
volume = "25",
doi = "10.1111/tbj.13326"
}

Kovač, M., Kovac, Z., Tomasević, Z., Tomić, B., Gvozdenov, M.,& Radojković, D.. (2019). Breast cancer and recurrent thrombosis - Results from prospective single center study. in Breast Journal
Wiley, Hoboken., 25(4), 783-785.
https://doi.org/10.1111/tbj.13326

Kovač M, Kovac Z, Tomasević Z, Tomić B, Gvozdenov M, Radojković D. Breast cancer and recurrent thrombosis - Results from prospective single center study. in Breast Journal. 2019;25(4):783-785.
doi:10.1111/tbj.13326 .

Kovač, Mirjana, Kovac, Zeljko, Tomasević, Zorica, Tomić, Branko, Gvozdenov, Maja, Radojković, Dragica, "Breast cancer and recurrent thrombosis - Results from prospective single center study" in Breast Journal, 25, no. 4 (2019):783-785,
https://doi.org/10.1111/tbj.13326 . .

TY  - JOUR
AU  - Babić, Tamara
AU  - Dinić, Jelena
AU  - Stojković Burić, Sonja
AU  - Hadzić, Stefan
AU  - Pesić, Milica
AU  - Radojković, Dragica
AU  - Divac Rankov, Aleksandra
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1132
AB  - Cancer drug resistance and poor selectivity towards cancer cells demand the constant search for new therapeutics. PI3K-Akt-mTOR and RAS-MAPK-ERK signaling pathways are key mechanisms involved in cell survival, proliferation, differentiation, and metabolism and their deregulation in cancer can promote development of therapy resistance. We investigated the effects of targeted inhibitors (wortmannin, GSK690693, AZD2014 and tipifarnib) towards these two pathways on early zebrafish and sea urchin development to assess their toxicity in normal, fast proliferating cells. PI3K inhibitor wortmannin and RAS inhibitor tipifarnib displayed highest toxicity while GSK690693, a pan-Akt kinase inhibitor, exhibited a less significant impact on embryo survival and development. Moreover, inhibition of the upstream part of the PI3K-Akt-mTOR pathway (wortmannin/GSK690693 co-treatment) produced a synergistic effect and impacted zebrafish embryo survival and development at much lower concentrations. Dual mTORC1/mTORC2 inhibitor AZD2014 showed no considerable effects on embryonic cells of zebrafish in concentrations substantially toxic in cancer cells. AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy.
PB  - Akademiai Kiado Zrt, Budapest
T2  - Acta Biologica Hungarica
T1  - Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models
EP  - 410
IS  - 4
SP  - 395
VL  - 69
DO  - 10.1556/018.69.2018.4.3
ER  - 

@article{
author = "Babić, Tamara and Dinić, Jelena and Stojković Burić, Sonja and Hadzić, Stefan and Pesić, Milica and Radojković, Dragica and Divac Rankov, Aleksandra",
year = "2018",
abstract = "Cancer drug resistance and poor selectivity towards cancer cells demand the constant search for new therapeutics. PI3K-Akt-mTOR and RAS-MAPK-ERK signaling pathways are key mechanisms involved in cell survival, proliferation, differentiation, and metabolism and their deregulation in cancer can promote development of therapy resistance. We investigated the effects of targeted inhibitors (wortmannin, GSK690693, AZD2014 and tipifarnib) towards these two pathways on early zebrafish and sea urchin development to assess their toxicity in normal, fast proliferating cells. PI3K inhibitor wortmannin and RAS inhibitor tipifarnib displayed highest toxicity while GSK690693, a pan-Akt kinase inhibitor, exhibited a less significant impact on embryo survival and development. Moreover, inhibition of the upstream part of the PI3K-Akt-mTOR pathway (wortmannin/GSK690693 co-treatment) produced a synergistic effect and impacted zebrafish embryo survival and development at much lower concentrations. Dual mTORC1/mTORC2 inhibitor AZD2014 showed no considerable effects on embryonic cells of zebrafish in concentrations substantially toxic in cancer cells. AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy.",
publisher = "Akademiai Kiado Zrt, Budapest",
journal = "Acta Biologica Hungarica",
title = "Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models",
pages = "410-395",
number = "4",
volume = "69",
doi = "10.1556/018.69.2018.4.3"
}

Babić, T., Dinić, J., Stojković Burić, S., Hadzić, S., Pesić, M., Radojković, D.,& Divac Rankov, A.. (2018). Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models. in Acta Biologica Hungarica
Akademiai Kiado Zrt, Budapest., 69(4), 395-410.
https://doi.org/10.1556/018.69.2018.4.3

Babić T, Dinić J, Stojković Burić S, Hadzić S, Pesić M, Radojković D, Divac Rankov A. Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models. in Acta Biologica Hungarica. 2018;69(4):395-410.
doi:10.1556/018.69.2018.4.3 .

Babić, Tamara, Dinić, Jelena, Stojković Burić, Sonja, Hadzić, Stefan, Pesić, Milica, Radojković, Dragica, Divac Rankov, Aleksandra, "Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models" in Acta Biologica Hungarica, 69, no. 4 (2018):395-410,
https://doi.org/10.1556/018.69.2018.4.3 . .

TY  - JOUR
AU  - Supić, Gordana
AU  - Zeljić, Katarina
AU  - Divac Rankov, Aleksandra
AU  - Kozomara, Ruzica
AU  - Nikolić, Aleksandra
AU  - Radojković, Dragica
AU  - Magić, Zvonko
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1162
AB  - Micro RNAs (miRNAs) have a major role in human cancerogenesis.The current study investigated the prognostic significance of miR-183 and miR-21 expression in tongue carcinoma patients. For qPCR of miR-183 and miR-21 expression, total RNA isolated from 60 fresh-frozen tissue of tongue carcinomas was converted into cDNA by TaqMan MicroRNA Reverse Transcription Kit and quantified by TaqMan MicroRNAs Expression Assays. Fold changes in the miRNAs expression, normalized to RNU6B, were determined using 2(-Delta Delta Ct) method, and dichotomized into high and low according to cut-off values derived from ROC curve analysis. miR-183 emerged as promising discriminatory biomarker of poor outcome. Tissue over-expression of miR-183, observed in 68.3% of tongue carcinomas, was associated with clinical stage (p = 0.037), tumor size (p = 0.036), and high alcohol intake (p = 0.034).The patients with miR-183 over-expression had significantly shorter overall survival (p = 0.006) and a 5.666 times higher risk of poor outcome (p = 0.005), while miR-21 over-expression carried a tendency towards poorer survival (p = 0.073). However, multivariate analysis revealed that the recurrences were independent adverse prognostic factors, while miR-183 over-expression lost its significance. Our results suggests that over-expression of miR-183 in tumor tissue could be a potential marker of clinical stage and a poor survival of tongue carcinoma patients and may be associated with high alcohol consumption. Oncogenic miRNAs, such as the investigated miR-183 and miR-21, could be novel prognostic biomarkers of tumor progression and adverse clinical outcome in oral cancer, as well as novel therapeutic targets in cancer.
PB  - Springer Heidelberg, Heidelberg
T2  - Clinical Oral Investigations
T1  - miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients
EP  - 409
IS  - 1
SP  - 401
VL  - 22
DO  - 10.1007/s00784-017-2126-y
ER  - 

@article{
author = "Supić, Gordana and Zeljić, Katarina and Divac Rankov, Aleksandra and Kozomara, Ruzica and Nikolić, Aleksandra and Radojković, Dragica and Magić, Zvonko",
year = "2018",
abstract = "Micro RNAs (miRNAs) have a major role in human cancerogenesis.The current study investigated the prognostic significance of miR-183 and miR-21 expression in tongue carcinoma patients. For qPCR of miR-183 and miR-21 expression, total RNA isolated from 60 fresh-frozen tissue of tongue carcinomas was converted into cDNA by TaqMan MicroRNA Reverse Transcription Kit and quantified by TaqMan MicroRNAs Expression Assays. Fold changes in the miRNAs expression, normalized to RNU6B, were determined using 2(-Delta Delta Ct) method, and dichotomized into high and low according to cut-off values derived from ROC curve analysis. miR-183 emerged as promising discriminatory biomarker of poor outcome. Tissue over-expression of miR-183, observed in 68.3% of tongue carcinomas, was associated with clinical stage (p = 0.037), tumor size (p = 0.036), and high alcohol intake (p = 0.034).The patients with miR-183 over-expression had significantly shorter overall survival (p = 0.006) and a 5.666 times higher risk of poor outcome (p = 0.005), while miR-21 over-expression carried a tendency towards poorer survival (p = 0.073). However, multivariate analysis revealed that the recurrences were independent adverse prognostic factors, while miR-183 over-expression lost its significance. Our results suggests that over-expression of miR-183 in tumor tissue could be a potential marker of clinical stage and a poor survival of tongue carcinoma patients and may be associated with high alcohol consumption. Oncogenic miRNAs, such as the investigated miR-183 and miR-21, could be novel prognostic biomarkers of tumor progression and adverse clinical outcome in oral cancer, as well as novel therapeutic targets in cancer.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Clinical Oral Investigations",
title = "miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients",
pages = "409-401",
number = "1",
volume = "22",
doi = "10.1007/s00784-017-2126-y"
}

Supić, G., Zeljić, K., Divac Rankov, A., Kozomara, R., Nikolić, A., Radojković, D.,& Magić, Z.. (2018). miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients. in Clinical Oral Investigations
Springer Heidelberg, Heidelberg., 22(1), 401-409.
https://doi.org/10.1007/s00784-017-2126-y

Supić G, Zeljić K, Divac Rankov A, Kozomara R, Nikolić A, Radojković D, Magić Z. miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients. in Clinical Oral Investigations. 2018;22(1):401-409.
doi:10.1007/s00784-017-2126-y .

Supić, Gordana, Zeljić, Katarina, Divac Rankov, Aleksandra, Kozomara, Ruzica, Nikolić, Aleksandra, Radojković, Dragica, Magić, Zvonko, "miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients" in Clinical Oral Investigations, 22, no. 1 (2018):401-409,
https://doi.org/10.1007/s00784-017-2126-y . .

TY  - JOUR
AU  - Bošković, Srđan
AU  - Marin-Juez, Ruben
AU  - Jasnić, Jovana
AU  - Reischauer, Sven
AU  - El Sammak, Hadil
AU  - Kojić, Ana
AU  - Faulkner, Georgine
AU  - Radojković, Dragica
AU  - Stainier, Didier Y. R.
AU  - Kojić, Snežana
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1141
AB  - Muscle proteins with ankyrin repeats (MARPs) ANKRD1 and ANKRD2 are titin-associated proteins with a putative role as transcriptional co-regulators in striated muscle, involved in the cellular response to mechanical, oxidative and metabolic stress. Since many aspects of the biology of MARPs, particularly exact mechanisms of their action, in striated muscle are still elusive, research in this field will benefit from novel animal model system. Here we investigated the MARPs found in zebrafish for protein structure, evolutionary conservation, spatiotemporal expression profiles and response to increased muscle activity. Ankrd1 and Ankrd2 show overall moderate conservation at the protein level, more pronounced in the region of ankyrin repeats, motifs indispensable for their function. The two zebrafish genes, ankrd1a and ankrd1b, counterparts of mammalian ANKRD1/Ankrd1, have different expression profiles during first seven days of development. Mild increase of ankrd1a transcript levels was detected at 72 hpf (1.74 +/- 0.24 fold increase relative to 24 hpf time point), while ankrd1b expression was markedly upregulated from 24 hpf onward and peaked at 72 hpf (92.18 +/- 36.95 fold increase relative to 24 hpf time point). Spatially, they exhibited non-overlapping expression patterns during skeletal muscle development in trunk (ankrd1a) and tail (ankrd1b) somites. Expression of ankrd2 was barely detectable. Zebrafish MARPs, expressed at a relatively low level in adult striated muscle, were found to be responsive to endurance exercise training consisting of two bouts of 3 hours of forced swimming daily, for five consecutive days. Three hours after the last exercise bout, ankrd1a expression increased in cardiac muscle (6.19 +/- 5.05 fold change), while ankrd1b and ankrd2 were upregulated in skeletal muscle (1.97 +/- 1.05 and 1.84 +/- 0.58 fold change, respectively). This study provides the foundation to establish zebrafish as a novel in vivo model for further investigation of MARPs function in striated muscle.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise
IS  - 9
VL  - 13
DO  - 10.1371/journal.pone.0204312
ER  - 

@article{
author = "Bošković, Srđan and Marin-Juez, Ruben and Jasnić, Jovana and Reischauer, Sven and El Sammak, Hadil and Kojić, Ana and Faulkner, Georgine and Radojković, Dragica and Stainier, Didier Y. R. and Kojić, Snežana",
year = "2018",
abstract = "Muscle proteins with ankyrin repeats (MARPs) ANKRD1 and ANKRD2 are titin-associated proteins with a putative role as transcriptional co-regulators in striated muscle, involved in the cellular response to mechanical, oxidative and metabolic stress. Since many aspects of the biology of MARPs, particularly exact mechanisms of their action, in striated muscle are still elusive, research in this field will benefit from novel animal model system. Here we investigated the MARPs found in zebrafish for protein structure, evolutionary conservation, spatiotemporal expression profiles and response to increased muscle activity. Ankrd1 and Ankrd2 show overall moderate conservation at the protein level, more pronounced in the region of ankyrin repeats, motifs indispensable for their function. The two zebrafish genes, ankrd1a and ankrd1b, counterparts of mammalian ANKRD1/Ankrd1, have different expression profiles during first seven days of development. Mild increase of ankrd1a transcript levels was detected at 72 hpf (1.74 +/- 0.24 fold increase relative to 24 hpf time point), while ankrd1b expression was markedly upregulated from 24 hpf onward and peaked at 72 hpf (92.18 +/- 36.95 fold increase relative to 24 hpf time point). Spatially, they exhibited non-overlapping expression patterns during skeletal muscle development in trunk (ankrd1a) and tail (ankrd1b) somites. Expression of ankrd2 was barely detectable. Zebrafish MARPs, expressed at a relatively low level in adult striated muscle, were found to be responsive to endurance exercise training consisting of two bouts of 3 hours of forced swimming daily, for five consecutive days. Three hours after the last exercise bout, ankrd1a expression increased in cardiac muscle (6.19 +/- 5.05 fold change), while ankrd1b and ankrd2 were upregulated in skeletal muscle (1.97 +/- 1.05 and 1.84 +/- 0.58 fold change, respectively). This study provides the foundation to establish zebrafish as a novel in vivo model for further investigation of MARPs function in striated muscle.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise",
number = "9",
volume = "13",
doi = "10.1371/journal.pone.0204312"
}

Bošković, S., Marin-Juez, R., Jasnić, J., Reischauer, S., El Sammak, H., Kojić, A., Faulkner, G., Radojković, D., Stainier, D. Y. R.,& Kojić, S.. (2018). Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise. in PLoS One
Public Library Science, San Francisco., 13(9).
https://doi.org/10.1371/journal.pone.0204312

Bošković S, Marin-Juez R, Jasnić J, Reischauer S, El Sammak H, Kojić A, Faulkner G, Radojković D, Stainier DYR, Kojić S. Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise. in PLoS One. 2018;13(9).
doi:10.1371/journal.pone.0204312 .

Bošković, Srđan, Marin-Juez, Ruben, Jasnić, Jovana, Reischauer, Sven, El Sammak, Hadil, Kojić, Ana, Faulkner, Georgine, Radojković, Dragica, Stainier, Didier Y. R., Kojić, Snežana, "Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise" in PLoS One, 13, no. 9 (2018),
https://doi.org/10.1371/journal.pone.0204312 . .

TY  - JOUR
AU  - Novković, Mirjana
AU  - Matić, Dragan
AU  - Kušić-Tišma, Jelena
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica
AU  - Rakićević, Ljiljana
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1187
AB  - Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C  gt  T, rs12248560), rs11568732 (c.-889T  gt  G, CYP2C19*20), CYP2C19*2 (c.681G  gt  A; rs4244285) and CYP2C19*3 (c.636G  gt  A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed. Association between bleeding (BARC type ae lt yen gt  2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings. Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.
PB  - Springer Heidelberg, Heidelberg
T2  - European Journal of Clinical Pharmacology
T1  - Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel
EP  - 451
IS  - 4
SP  - 443
VL  - 74
DO  - 10.1007/s00228-017-2401-5
ER  - 

@article{
author = "Novković, Mirjana and Matić, Dragan and Kušić-Tišma, Jelena and Antonijević, Nebojša and Radojković, Dragica and Rakićević, Ljiljana",
year = "2018",
abstract = "Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C  gt  T, rs12248560), rs11568732 (c.-889T  gt  G, CYP2C19*20), CYP2C19*2 (c.681G  gt  A; rs4244285) and CYP2C19*3 (c.636G  gt  A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed. Association between bleeding (BARC type ae lt yen gt  2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings. Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "European Journal of Clinical Pharmacology",
title = "Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel",
pages = "451-443",
number = "4",
volume = "74",
doi = "10.1007/s00228-017-2401-5"
}

Novković, M., Matić, D., Kušić-Tišma, J., Antonijević, N., Radojković, D.,& Rakićević, L.. (2018). Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel. in European Journal of Clinical Pharmacology
Springer Heidelberg, Heidelberg., 74(4), 443-451.
https://doi.org/10.1007/s00228-017-2401-5

Novković M, Matić D, Kušić-Tišma J, Antonijević N, Radojković D, Rakićević L. Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel. in European Journal of Clinical Pharmacology. 2018;74(4):443-451.
doi:10.1007/s00228-017-2401-5 .

Novković, Mirjana, Matić, Dragan, Kušić-Tišma, Jelena, Antonijević, Nebojša, Radojković, Dragica, Rakićević, Ljiljana, "Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel" in European Journal of Clinical Pharmacology, 74, no. 4 (2018):443-451,
https://doi.org/10.1007/s00228-017-2401-5 . .

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 .