Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects

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Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects (en)
Ретке болести: молекуларна патофизиологија, дијагностички и терапијски модалитети и социјални, етички и правни аспекти (sr)
Retke bolesti: molekularna patofiziologija, dijagnostički i terapijski modaliteti i socijalni, etički i pravni aspekti (sr_RS)
Authors

Publications

Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.

Spasovski, Vesna; Srzentić Dražilov, Sanja; Nikčević, Gordana; Baščarević, Zoran; Stojiljković, Maja; Pavlović, Sonja; Spasovski, Duško

(MDPI, 2023)

TY  - DATA
AU  - Spasovski, Vesna
AU  - Srzentić Dražilov, Sanja
AU  - Nikčević, Gordana
AU  - Baščarević, Zoran
AU  - Stojiljković, Maja
AU  - Pavlović, Sonja
AU  - Spasovski, Duško
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2089
AB  - Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.
PB  - MDPI
T2  - Diagnostics
T1  - Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.
IS  - 3
SP  - 471
VL  - 13
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2089
ER  - 
@misc{
author = "Spasovski, Vesna and Srzentić Dražilov, Sanja and Nikčević, Gordana and Baščarević, Zoran and Stojiljković, Maja and Pavlović, Sonja and Spasovski, Duško",
year = "2023",
abstract = "Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.",
publisher = "MDPI",
journal = "Diagnostics",
title = "Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.",
number = "3",
pages = "471",
volume = "13",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2089"
}
Spasovski, V., Srzentić Dražilov, S., Nikčević, G., Baščarević, Z., Stojiljković, M., Pavlović, S.,& Spasovski, D.. (2023). Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.. in Diagnostics
MDPI., 13(3), 471.
https://hdl.handle.net/21.15107/rcub_imagine_2089
Spasovski V, Srzentić Dražilov S, Nikčević G, Baščarević Z, Stojiljković M, Pavlović S, Spasovski D. Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.. in Diagnostics. 2023;13(3):471.
https://hdl.handle.net/21.15107/rcub_imagine_2089 .
Spasovski, Vesna, Srzentić Dražilov, Sanja, Nikčević, Gordana, Baščarević, Zoran, Stojiljković, Maja, Pavlović, Sonja, Spasovski, Duško, "Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471." in Diagnostics, 13, no. 3 (2023):471,
https://hdl.handle.net/21.15107/rcub_imagine_2089 .

Molecular Biomarkers in Perthes Disease: A Review

Spasovski, Vesna; Srzentić Dražilov, Sanja; Nikčević, Gordana; Baščarević, Zoran; Stojiljković, Maja; Pavlović, Sonja; Spasovski, Duško

(MDPI, 2023)

TY  - JOUR
AU  - Spasovski, Vesna
AU  - Srzentić Dražilov, Sanja
AU  - Nikčević, Gordana
AU  - Baščarević, Zoran
AU  - Stojiljković, Maja
AU  - Pavlović, Sonja
AU  - Spasovski, Duško
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2088
AB  - Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.
PB  - MDPI
T2  - Diagnostics
T1  - Molecular Biomarkers in Perthes Disease: A Review
IS  - 3
SP  - 471
VL  - 13
DO  - 10.3390/diagnostics13030471
ER  - 
@article{
author = "Spasovski, Vesna and Srzentić Dražilov, Sanja and Nikčević, Gordana and Baščarević, Zoran and Stojiljković, Maja and Pavlović, Sonja and Spasovski, Duško",
year = "2023",
abstract = "Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.",
publisher = "MDPI",
journal = "Diagnostics",
title = "Molecular Biomarkers in Perthes Disease: A Review",
number = "3",
pages = "471",
volume = "13",
doi = "10.3390/diagnostics13030471"
}
Spasovski, V., Srzentić Dražilov, S., Nikčević, G., Baščarević, Z., Stojiljković, M., Pavlović, S.,& Spasovski, D.. (2023). Molecular Biomarkers in Perthes Disease: A Review. in Diagnostics
MDPI., 13(3), 471.
https://doi.org/10.3390/diagnostics13030471
Spasovski V, Srzentić Dražilov S, Nikčević G, Baščarević Z, Stojiljković M, Pavlović S, Spasovski D. Molecular Biomarkers in Perthes Disease: A Review. in Diagnostics. 2023;13(3):471.
doi:10.3390/diagnostics13030471 .
Spasovski, Vesna, Srzentić Dražilov, Sanja, Nikčević, Gordana, Baščarević, Zoran, Stojiljković, Maja, Pavlović, Sonja, Spasovski, Duško, "Molecular Biomarkers in Perthes Disease: A Review" in Diagnostics, 13, no. 3 (2023):471,
https://doi.org/10.3390/diagnostics13030471 . .
1
4
3

Molekularni profil timoma

Perić, Jelena

(Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo, 2022)

TY  - CHAP
AU  - Perić, Jelena
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1818
AB  - Timomi, timusni karcinomi (TC) i timusni neuroendokrini kanceri su najčešce neoplazije lokalizovane
u timusu i pripadaju retkim formama tumora. Timomi su indolentne forme tumora, a klasifikovani su u A,
AB, B1,B2, B3 kategorije. Novije genetičke studije timoma pokazale su da je jedan od dominantnih markera
ove bolesti , gen GTF2I sa najčešćim ’drajver’ varijantama Chr7 c.1211T> A, p. Leu404His i c.1271T>A, p.
Leu424His. Pored GTF2I, u patogenezu timoma su uključeni EGFR, TP53, kao i Ras signalni putevi. Molekularna
pozadina timoma jos uvek nije dovoljno istražena, međutim sa sve većim napretkom novih tehnologija,
poput sekvenciranja nove generacije (eng. NGS) došlo se do novih informacija koje ukazuju na
uzrok, detektuju nove molekularne markere, a samim tim omogućuju uspešnije terapijske pristupe ovoj
patologiji.
AB  - Thymoma, thymic carcinoma (TC), and thymic neuroendocrine carcinoma are rare thymic epithelial
tumors (TETs) and the most frequent thymus-specific neoplasia. Thymomas are indolent or the
less aggressive forms of TETs classified into the following subgroups A, AB, B1, B2, and B3. The most
recent studies suggest thymoma specific gene GTF2I, with Chr7 c.1211T> A, p. Leu404His and
c.1271T>A, p. Leu424His, is considered driver variants for this disease. Additionally, in thymoma pathogenesis
are included EGFR, TP53 and Ras signaling pathways. The molecular background of thymoma
is still obscure, but the advance of new technologies such as next-generation sequencing (eng.
NGS) brings new information related to the molecular milieu of thymoma and other cancers. New information
help to explore the cause of the disease, detection of new molecular markers, and better
therapy approaches for thymoma.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Treći kongres biologa Srbije
T1  - Molekularni profil timoma
T1  - Molecular profile of thymoma
EP  - 153
IS  - 2
SP  - 143
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1818
ER  - 
@inbook{
author = "Perić, Jelena",
year = "2022",
abstract = "Timomi, timusni karcinomi (TC) i timusni neuroendokrini kanceri su najčešce neoplazije lokalizovane
u timusu i pripadaju retkim formama tumora. Timomi su indolentne forme tumora, a klasifikovani su u A,
AB, B1,B2, B3 kategorije. Novije genetičke studije timoma pokazale su da je jedan od dominantnih markera
ove bolesti , gen GTF2I sa najčešćim ’drajver’ varijantama Chr7 c.1211T> A, p. Leu404His i c.1271T>A, p.
Leu424His. Pored GTF2I, u patogenezu timoma su uključeni EGFR, TP53, kao i Ras signalni putevi. Molekularna
pozadina timoma jos uvek nije dovoljno istražena, međutim sa sve većim napretkom novih tehnologija,
poput sekvenciranja nove generacije (eng. NGS) došlo se do novih informacija koje ukazuju na
uzrok, detektuju nove molekularne markere, a samim tim omogućuju uspešnije terapijske pristupe ovoj
patologiji., Thymoma, thymic carcinoma (TC), and thymic neuroendocrine carcinoma are rare thymic epithelial
tumors (TETs) and the most frequent thymus-specific neoplasia. Thymomas are indolent or the
less aggressive forms of TETs classified into the following subgroups A, AB, B1, B2, and B3. The most
recent studies suggest thymoma specific gene GTF2I, with Chr7 c.1211T> A, p. Leu404His and
c.1271T>A, p. Leu424His, is considered driver variants for this disease. Additionally, in thymoma pathogenesis
are included EGFR, TP53 and Ras signaling pathways. The molecular background of thymoma
is still obscure, but the advance of new technologies such as next-generation sequencing (eng.
NGS) brings new information related to the molecular milieu of thymoma and other cancers. New information
help to explore the cause of the disease, detection of new molecular markers, and better
therapy approaches for thymoma.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Treći kongres biologa Srbije",
booktitle = "Molekularni profil timoma, Molecular profile of thymoma",
pages = "153-143",
number = "2",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1818"
}
Perić, J.. (2022). Molekularni profil timoma. in Treći kongres biologa Srbije
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo.(2), 143-153.
https://hdl.handle.net/21.15107/rcub_imagine_1818
Perić J. Molekularni profil timoma. in Treći kongres biologa Srbije. 2022;(2):143-153.
https://hdl.handle.net/21.15107/rcub_imagine_1818 .
Perić, Jelena, "Molekularni profil timoma" in Treći kongres biologa Srbije, no. 2 (2022):143-153,
https://hdl.handle.net/21.15107/rcub_imagine_1818 .

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia

Buha, I.; Škodrić-Trifunović, V.; Anđelković, Marina; Pavlović, Sonja; Vreća, M.; Stjepanović, M.; Milin-Lazović, Jelena; Simić, M.; Antonijević, G.; Spasovski, Vesna

(Journal of Infection in Developing Countries, 2022)

TY  - JOUR
AU  - Buha, I.
AU  - Škodrić-Trifunović, V.
AU  - Anđelković, Marina
AU  - Pavlović, Sonja
AU  - Vreća, M.
AU  - Stjepanović, M.
AU  - Milin-Lazović, Jelena
AU  - Simić, M.
AU  - Antonijević, G.
AU  - Spasovski, Vesna
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1542
AB  - Introduction: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. Methodology: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. Results: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. Conclusions: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.
PB  - Journal of Infection in Developing Countries
T2  - Journal of Infection in Developing Countries
T1  - Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia
EP  - 1332
IS  - 8
SP  - 1317
VL  - 16
DO  - 10.3855/jidc.16721
ER  - 
@article{
author = "Buha, I. and Škodrić-Trifunović, V. and Anđelković, Marina and Pavlović, Sonja and Vreća, M. and Stjepanović, M. and Milin-Lazović, Jelena and Simić, M. and Antonijević, G. and Spasovski, Vesna",
year = "2022",
abstract = "Introduction: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. Methodology: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. Results: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. Conclusions: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.",
publisher = "Journal of Infection in Developing Countries",
journal = "Journal of Infection in Developing Countries",
title = "Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia",
pages = "1332-1317",
number = "8",
volume = "16",
doi = "10.3855/jidc.16721"
}
Buha, I., Škodrić-Trifunović, V., Anđelković, M., Pavlović, S., Vreća, M., Stjepanović, M., Milin-Lazović, J., Simić, M., Antonijević, G.,& Spasovski, V.. (2022). Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia. in Journal of Infection in Developing Countries
Journal of Infection in Developing Countries., 16(8), 1317-1332.
https://doi.org/10.3855/jidc.16721
Buha I, Škodrić-Trifunović V, Anđelković M, Pavlović S, Vreća M, Stjepanović M, Milin-Lazović J, Simić M, Antonijević G, Spasovski V. Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia. in Journal of Infection in Developing Countries. 2022;16(8):1317-1332.
doi:10.3855/jidc.16721 .
Buha, I., Škodrić-Trifunović, V., Anđelković, Marina, Pavlović, Sonja, Vreća, M., Stjepanović, M., Milin-Lazović, Jelena, Simić, M., Antonijević, G., Spasovski, Vesna, "Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia" in Journal of Infection in Developing Countries, 16, no. 8 (2022):1317-1332,
https://doi.org/10.3855/jidc.16721 . .
2
2

Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra

Mihaljević, Biljana; Vuković, Vojin; Milić, Nataša; Karan-Đurašević, Teodora; Tošić, Nataša; Kostić, Tatjana; Marjanović, Irena; Denčić-Fekete, Marija; Đurašinović, Vladislava; Dragović-Ivančević, Tijana; Pavlović, Sonja; Antić, Darko

(Srpsko lekarsko društvo, Beograd, 2021)

TY  - JOUR
AU  - Mihaljević, Biljana
AU  - Vuković, Vojin
AU  - Milić, Nataša
AU  - Karan-Đurašević, Teodora
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Denčić-Fekete, Marija
AU  - Đurašinović, Vladislava
AU  - Dragović-Ivančević, Tijana
AU  - Pavlović, Sonja
AU  - Antić, Darko
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1458
AB  - Uvod/Cilj Prognoza hronične limfocitne leukemije (HLL) značajno je unapređena u poslednje vreme. Među nekoliko prognostičkih modela čiji je cilj predviđanje vremena do prve terapije (eng. TTFT) izdvajaju se skor rizika od progresije (eng. PRS) i skor Centra za rak MD Anderson iz 2011. God. (eng. MDACC 2011), dok se internacionalni prognostički indeks za HLL (eng. CLL-IPI), iako primarno ustanovljen za predikciju ukupnog preživljavanja (eng. OS), dobro pokazao i u predikciji TTFT. Cilj ovog rada je da se ispita značaj pomenutih prognostičkih modela u pogledu predviđanja TTFT i OS. Metode Analizirana kohorta je obuhvatila 57 neselektovanih bolesnika sa HLL Univerzitetskog kliničkog centra Srbije sa prosečno agresivnijim profilom bolesti u odnosu na opštu populaciju de novo bolesnika sa HLL. Bolesnici su ocenjivani prema navedenim skorovima uz analizu TTFT i OS. Rezultati Bolesnici sa višim vrednostima CLL-IPI, PRS i MDACC 2011 primili su prvu terapiju značajno ranije u poređenju sa bolesnicima sa nižim vrednostima ovih skorova (p = 0,002, p = 0,019 i p  lt  0,001, redom). U multivarijantnoj analizi, MDACC 2011 i CLL-IPI su zadržali prognostički značaj u predikciji TTFT (p = 0,001, odnosno p = 0,018), dok je PRS ovaj značaj izgubio. CLL-IPI je bio jedini značajan prediktor OS u univarijantnoj (p = 0,005) i u multivarijantnoj analizi (p = 0,013). Zaključak CLL-IPI, PRS i naročito MDACC 2011 su dobri prediktori TTFT čak i u kohortama bolesnika sa agresivnijom bolešću, dok je za predikciju OS od ova tri prognostička modela CLL-IPI jedini primenljiv. Ovi rezultati pokazuju da bi prognostičke modele trebalo ispitati na bolesnicima sa HLL u različitim fazama bolesti, kakvi se sreću u realnoj kliničkoj praksi.
AB  - Introduction/Objective Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), progression-risk score (PRS), and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in the general de novo CLL population. The eligible patients were assigned investigated PMs, and TTFT and OS analyses were performed. Results Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p  lt  0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that PMs should be investigated in more diverse CLL populations, as it is in real-life setting.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra
T1  - Comparative analysis of International Prognostic Index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score: A single center experience
EP  - 421
IS  - 7-8
SP  - 415
VL  - 149
DO  - 10.2298/SARH201005047M
ER  - 
@article{
author = "Mihaljević, Biljana and Vuković, Vojin and Milić, Nataša and Karan-Đurašević, Teodora and Tošić, Nataša and Kostić, Tatjana and Marjanović, Irena and Denčić-Fekete, Marija and Đurašinović, Vladislava and Dragović-Ivančević, Tijana and Pavlović, Sonja and Antić, Darko",
year = "2021",
abstract = "Uvod/Cilj Prognoza hronične limfocitne leukemije (HLL) značajno je unapređena u poslednje vreme. Među nekoliko prognostičkih modela čiji je cilj predviđanje vremena do prve terapije (eng. TTFT) izdvajaju se skor rizika od progresije (eng. PRS) i skor Centra za rak MD Anderson iz 2011. God. (eng. MDACC 2011), dok se internacionalni prognostički indeks za HLL (eng. CLL-IPI), iako primarno ustanovljen za predikciju ukupnog preživljavanja (eng. OS), dobro pokazao i u predikciji TTFT. Cilj ovog rada je da se ispita značaj pomenutih prognostičkih modela u pogledu predviđanja TTFT i OS. Metode Analizirana kohorta je obuhvatila 57 neselektovanih bolesnika sa HLL Univerzitetskog kliničkog centra Srbije sa prosečno agresivnijim profilom bolesti u odnosu na opštu populaciju de novo bolesnika sa HLL. Bolesnici su ocenjivani prema navedenim skorovima uz analizu TTFT i OS. Rezultati Bolesnici sa višim vrednostima CLL-IPI, PRS i MDACC 2011 primili su prvu terapiju značajno ranije u poređenju sa bolesnicima sa nižim vrednostima ovih skorova (p = 0,002, p = 0,019 i p  lt  0,001, redom). U multivarijantnoj analizi, MDACC 2011 i CLL-IPI su zadržali prognostički značaj u predikciji TTFT (p = 0,001, odnosno p = 0,018), dok je PRS ovaj značaj izgubio. CLL-IPI je bio jedini značajan prediktor OS u univarijantnoj (p = 0,005) i u multivarijantnoj analizi (p = 0,013). Zaključak CLL-IPI, PRS i naročito MDACC 2011 su dobri prediktori TTFT čak i u kohortama bolesnika sa agresivnijom bolešću, dok je za predikciju OS od ova tri prognostička modela CLL-IPI jedini primenljiv. Ovi rezultati pokazuju da bi prognostičke modele trebalo ispitati na bolesnicima sa HLL u različitim fazama bolesti, kakvi se sreću u realnoj kliničkoj praksi., Introduction/Objective Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), progression-risk score (PRS), and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in the general de novo CLL population. The eligible patients were assigned investigated PMs, and TTFT and OS analyses were performed. Results Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p  lt  0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that PMs should be investigated in more diverse CLL populations, as it is in real-life setting.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra, Comparative analysis of International Prognostic Index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score: A single center experience",
pages = "421-415",
number = "7-8",
volume = "149",
doi = "10.2298/SARH201005047M"
}
Mihaljević, B., Vuković, V., Milić, N., Karan-Đurašević, T., Tošić, N., Kostić, T., Marjanović, I., Denčić-Fekete, M., Đurašinović, V., Dragović-Ivančević, T., Pavlović, S.,& Antić, D.. (2021). Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 149(7-8), 415-421.
https://doi.org/10.2298/SARH201005047M
Mihaljević B, Vuković V, Milić N, Karan-Đurašević T, Tošić N, Kostić T, Marjanović I, Denčić-Fekete M, Đurašinović V, Dragović-Ivančević T, Pavlović S, Antić D. Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo. 2021;149(7-8):415-421.
doi:10.2298/SARH201005047M .
Mihaljević, Biljana, Vuković, Vojin, Milić, Nataša, Karan-Đurašević, Teodora, Tošić, Nataša, Kostić, Tatjana, Marjanović, Irena, Denčić-Fekete, Marija, Đurašinović, Vladislava, Dragović-Ivančević, Tijana, Pavlović, Sonja, Antić, Darko, "Uporedna analiza internacionalnog prognostičkog indeksa za hroničnu limfocitnu leukemiju, skora rizika od progresije i skora Centra za rak MD Anderson - iskustvo jednog centra" in Srpski arhiv za celokupno lekarstvo, 149, no. 7-8 (2021):415-421,
https://doi.org/10.2298/SARH201005047M . .

alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population

Loncarić, Darija; Rodriguez, Laura; Debeissat, Christelle; Touya, Nicolas; Labat, Veronique; Villacreces, Arnaud; Bouzier-Sore, Anne-Karine; Pasquet, Jean-Max; de la Grange, Philippe Brunet; Vlaski-Lafarge, Marija; Pavlović, Sonja; Ivanović, Zoran

(Springer, New York, 2021)

TY  - JOUR
AU  - Loncarić, Darija
AU  - Rodriguez, Laura
AU  - Debeissat, Christelle
AU  - Touya, Nicolas
AU  - Labat, Veronique
AU  - Villacreces, Arnaud
AU  - Bouzier-Sore, Anne-Karine
AU  - Pasquet, Jean-Max
AU  - de la Grange, Philippe Brunet
AU  - Vlaski-Lafarge, Marija
AU  - Pavlović, Sonja
AU  - Ivanović, Zoran
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1754
AB  - We present here the data showing, in standard cultures exposed to atmospheric O-2 concentration, that alpha-tocopherol acetate (alpha-TOA) has a positive impact on primitive cells inside mesenchymal stromal cell (MstroC) population, by maintaining their proliferative capacity. alpha-TOA decreases the O-2 consumption rate of MStroC probably by impacting respiratory chain complex II activity. This action, however, is not associated with a compensatory increase in glycolysis activity, in spite of the fact that the degradation of HIF-1 alpha was decreased in presence of alpha-TOA. This is in line with a moderate enhancement of mtROS upon alpha-TOA treatment. However, the absence of glycolysis stimulation implies the inactivity of HIF-1 alpha which might - if it were active - be related to the maintenance of stemness. It should be stressed that alpha-TOA might act directly on the gene expression as well as the mtROS themselves, which remains to be elucidated.
PB  - Springer, New York
T2  - Stem Cell Reviews and Reports
T1  - alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population
EP  - 1405
IS  - 4
SP  - 1390
VL  - 17
DO  - 10.1007/s12015-020-10111-9
ER  - 
@article{
author = "Loncarić, Darija and Rodriguez, Laura and Debeissat, Christelle and Touya, Nicolas and Labat, Veronique and Villacreces, Arnaud and Bouzier-Sore, Anne-Karine and Pasquet, Jean-Max and de la Grange, Philippe Brunet and Vlaski-Lafarge, Marija and Pavlović, Sonja and Ivanović, Zoran",
year = "2021",
abstract = "We present here the data showing, in standard cultures exposed to atmospheric O-2 concentration, that alpha-tocopherol acetate (alpha-TOA) has a positive impact on primitive cells inside mesenchymal stromal cell (MstroC) population, by maintaining their proliferative capacity. alpha-TOA decreases the O-2 consumption rate of MStroC probably by impacting respiratory chain complex II activity. This action, however, is not associated with a compensatory increase in glycolysis activity, in spite of the fact that the degradation of HIF-1 alpha was decreased in presence of alpha-TOA. This is in line with a moderate enhancement of mtROS upon alpha-TOA treatment. However, the absence of glycolysis stimulation implies the inactivity of HIF-1 alpha which might - if it were active - be related to the maintenance of stemness. It should be stressed that alpha-TOA might act directly on the gene expression as well as the mtROS themselves, which remains to be elucidated.",
publisher = "Springer, New York",
journal = "Stem Cell Reviews and Reports",
title = "alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population",
pages = "1405-1390",
number = "4",
volume = "17",
doi = "10.1007/s12015-020-10111-9"
}
Loncarić, D., Rodriguez, L., Debeissat, C., Touya, N., Labat, V., Villacreces, A., Bouzier-Sore, A., Pasquet, J., de la Grange, P. B., Vlaski-Lafarge, M., Pavlović, S.,& Ivanović, Z.. (2021). alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population. in Stem Cell Reviews and Reports
Springer, New York., 17(4), 1390-1405.
https://doi.org/10.1007/s12015-020-10111-9
Loncarić D, Rodriguez L, Debeissat C, Touya N, Labat V, Villacreces A, Bouzier-Sore A, Pasquet J, de la Grange PB, Vlaski-Lafarge M, Pavlović S, Ivanović Z. alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population. in Stem Cell Reviews and Reports. 2021;17(4):1390-1405.
doi:10.1007/s12015-020-10111-9 .
Loncarić, Darija, Rodriguez, Laura, Debeissat, Christelle, Touya, Nicolas, Labat, Veronique, Villacreces, Arnaud, Bouzier-Sore, Anne-Karine, Pasquet, Jean-Max, de la Grange, Philippe Brunet, Vlaski-Lafarge, Marija, Pavlović, Sonja, Ivanović, Zoran, "alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population" in Stem Cell Reviews and Reports, 17, no. 4 (2021):1390-1405,
https://doi.org/10.1007/s12015-020-10111-9 . .
3
1
3

alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population

Loncarić, Darija; Rodriguez, Laura; Debeissat, Christelle; Touya, Nicolas; Labat, Veronique; Villacreces, Arnaud; Bouzier-Sore, Anne-Karine; Pasquet, Jean-Max; de la Grange, Philippe Brunet; Vlaski-Lafarge, Marija; Pavlović, Sonja; Ivanović, Zoran

(Springer, New York, 2021)

TY  - JOUR
AU  - Loncarić, Darija
AU  - Rodriguez, Laura
AU  - Debeissat, Christelle
AU  - Touya, Nicolas
AU  - Labat, Veronique
AU  - Villacreces, Arnaud
AU  - Bouzier-Sore, Anne-Karine
AU  - Pasquet, Jean-Max
AU  - de la Grange, Philippe Brunet
AU  - Vlaski-Lafarge, Marija
AU  - Pavlović, Sonja
AU  - Ivanović, Zoran
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1491
AB  - We present here the data showing, in standard cultures exposed to atmospheric O-2 concentration, that alpha-tocopherol acetate (alpha-TOA) has a positive impact on primitive cells inside mesenchymal stromal cell (MstroC) population, by maintaining their proliferative capacity. alpha-TOA decreases the O-2 consumption rate of MStroC probably by impacting respiratory chain complex II activity. This action, however, is not associated with a compensatory increase in glycolysis activity, in spite of the fact that the degradation of HIF-1 alpha was decreased in presence of alpha-TOA. This is in line with a moderate enhancement of mtROS upon alpha-TOA treatment. However, the absence of glycolysis stimulation implies the inactivity of HIF-1 alpha which might - if it were active - be related to the maintenance of stemness. It should be stressed that alpha-TOA might act directly on the gene expression as well as the mtROS themselves, which remains to be elucidated.
PB  - Springer, New York
T2  - Stem Cell Reviews and Reports
T1  - alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population
EP  - 1405
IS  - 4
SP  - 1390
VL  - 17
DO  - 10.1007/s12015-020-10111-9
ER  - 
@article{
author = "Loncarić, Darija and Rodriguez, Laura and Debeissat, Christelle and Touya, Nicolas and Labat, Veronique and Villacreces, Arnaud and Bouzier-Sore, Anne-Karine and Pasquet, Jean-Max and de la Grange, Philippe Brunet and Vlaski-Lafarge, Marija and Pavlović, Sonja and Ivanović, Zoran",
year = "2021",
abstract = "We present here the data showing, in standard cultures exposed to atmospheric O-2 concentration, that alpha-tocopherol acetate (alpha-TOA) has a positive impact on primitive cells inside mesenchymal stromal cell (MstroC) population, by maintaining their proliferative capacity. alpha-TOA decreases the O-2 consumption rate of MStroC probably by impacting respiratory chain complex II activity. This action, however, is not associated with a compensatory increase in glycolysis activity, in spite of the fact that the degradation of HIF-1 alpha was decreased in presence of alpha-TOA. This is in line with a moderate enhancement of mtROS upon alpha-TOA treatment. However, the absence of glycolysis stimulation implies the inactivity of HIF-1 alpha which might - if it were active - be related to the maintenance of stemness. It should be stressed that alpha-TOA might act directly on the gene expression as well as the mtROS themselves, which remains to be elucidated.",
publisher = "Springer, New York",
journal = "Stem Cell Reviews and Reports",
title = "alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population",
pages = "1405-1390",
number = "4",
volume = "17",
doi = "10.1007/s12015-020-10111-9"
}
Loncarić, D., Rodriguez, L., Debeissat, C., Touya, N., Labat, V., Villacreces, A., Bouzier-Sore, A., Pasquet, J., de la Grange, P. B., Vlaski-Lafarge, M., Pavlović, S.,& Ivanović, Z.. (2021). alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population. in Stem Cell Reviews and Reports
Springer, New York., 17(4), 1390-1405.
https://doi.org/10.1007/s12015-020-10111-9
Loncarić D, Rodriguez L, Debeissat C, Touya N, Labat V, Villacreces A, Bouzier-Sore A, Pasquet J, de la Grange PB, Vlaski-Lafarge M, Pavlović S, Ivanović Z. alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population. in Stem Cell Reviews and Reports. 2021;17(4):1390-1405.
doi:10.1007/s12015-020-10111-9 .
Loncarić, Darija, Rodriguez, Laura, Debeissat, Christelle, Touya, Nicolas, Labat, Veronique, Villacreces, Arnaud, Bouzier-Sore, Anne-Karine, Pasquet, Jean-Max, de la Grange, Philippe Brunet, Vlaski-Lafarge, Marija, Pavlović, Sonja, Ivanović, Zoran, "alpha-Tocopherol Acetate Attenuates Mitochondrial Oxygen Consumption and Maintains Primitive Cells within Mesenchymal Stromal Cell Population" in Stem Cell Reviews and Reports, 17, no. 4 (2021):1390-1405,
https://doi.org/10.1007/s12015-020-10111-9 . .
3
1
3

Case Report: Successful Therapy of Spontaneously Occurring Canine Degenerative Lumbosacral Stenosis Using Autologous Adipose Tissue-Derived Mesenchymal Stem Cells

Mrkovacki, Janko; Srzentić Dražilov, Sanja; Spasovski, Vesna; Fazlagić, Amira; Pavlović, Sonja; Nikčević, Gordana

(Frontiers Media Sa, Lausanne, 2021)

TY  - JOUR
AU  - Mrkovacki, Janko
AU  - Srzentić Dražilov, Sanja
AU  - Spasovski, Vesna
AU  - Fazlagić, Amira
AU  - Pavlović, Sonja
AU  - Nikčević, Gordana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1476
AB  - The management of degenerative lumbosacral stenosis (DLSS) in dogs usually requires aggressive, costly surgical treatments that may themselves present complications, while do not fully resolve the symptoms of the disease. In this study, the dog diagnosed with severe DLSS, with hind limb paresis, was treated using a new and least invasive treatment. Cultured autologous adipose tissue-derived mesenchymal stem cells (AT-MSCs) were injected bilaterally at the level of L7-S1, in the vicinity of the external aperture of the intervertebral foramen of DLSS patient. In the previously described treatments of spontaneous intervertebral disc degeneration in dogs, intradiscal injections of MSCs did not lead to positive effects. Here, we report a marked improvement in clinical outcome measures related to the ability of a dog to walk and trot, which were expressed by a numeric rating scale based on a veterinary assessment questionnaire. The improved status persisted throughout the observed time course of 4.5 years after the AT-MSC transplantation. To the best of our knowledge, this is the first case of successful therapy, with long-term positive effect, of spontaneously occurring canine DLSS using presented treatment that, we believe, represents a contribution to current knowledge in this field and may shape both animal and human DLSS treatment options.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Veterinary Science
T1  - Case Report: Successful Therapy of Spontaneously Occurring Canine Degenerative Lumbosacral Stenosis Using Autologous Adipose Tissue-Derived Mesenchymal Stem Cells
VL  - 8
DO  - 10.3389/fvets.2021.732073
ER  - 
@article{
author = "Mrkovacki, Janko and Srzentić Dražilov, Sanja and Spasovski, Vesna and Fazlagić, Amira and Pavlović, Sonja and Nikčević, Gordana",
year = "2021",
abstract = "The management of degenerative lumbosacral stenosis (DLSS) in dogs usually requires aggressive, costly surgical treatments that may themselves present complications, while do not fully resolve the symptoms of the disease. In this study, the dog diagnosed with severe DLSS, with hind limb paresis, was treated using a new and least invasive treatment. Cultured autologous adipose tissue-derived mesenchymal stem cells (AT-MSCs) were injected bilaterally at the level of L7-S1, in the vicinity of the external aperture of the intervertebral foramen of DLSS patient. In the previously described treatments of spontaneous intervertebral disc degeneration in dogs, intradiscal injections of MSCs did not lead to positive effects. Here, we report a marked improvement in clinical outcome measures related to the ability of a dog to walk and trot, which were expressed by a numeric rating scale based on a veterinary assessment questionnaire. The improved status persisted throughout the observed time course of 4.5 years after the AT-MSC transplantation. To the best of our knowledge, this is the first case of successful therapy, with long-term positive effect, of spontaneously occurring canine DLSS using presented treatment that, we believe, represents a contribution to current knowledge in this field and may shape both animal and human DLSS treatment options.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Veterinary Science",
title = "Case Report: Successful Therapy of Spontaneously Occurring Canine Degenerative Lumbosacral Stenosis Using Autologous Adipose Tissue-Derived Mesenchymal Stem Cells",
volume = "8",
doi = "10.3389/fvets.2021.732073"
}
Mrkovacki, J., Srzentić Dražilov, S., Spasovski, V., Fazlagić, A., Pavlović, S.,& Nikčević, G.. (2021). Case Report: Successful Therapy of Spontaneously Occurring Canine Degenerative Lumbosacral Stenosis Using Autologous Adipose Tissue-Derived Mesenchymal Stem Cells. in Frontiers in Veterinary Science
Frontiers Media Sa, Lausanne., 8.
https://doi.org/10.3389/fvets.2021.732073
Mrkovacki J, Srzentić Dražilov S, Spasovski V, Fazlagić A, Pavlović S, Nikčević G. Case Report: Successful Therapy of Spontaneously Occurring Canine Degenerative Lumbosacral Stenosis Using Autologous Adipose Tissue-Derived Mesenchymal Stem Cells. in Frontiers in Veterinary Science. 2021;8.
doi:10.3389/fvets.2021.732073 .
Mrkovacki, Janko, Srzentić Dražilov, Sanja, Spasovski, Vesna, Fazlagić, Amira, Pavlović, Sonja, Nikčević, Gordana, "Case Report: Successful Therapy of Spontaneously Occurring Canine Degenerative Lumbosacral Stenosis Using Autologous Adipose Tissue-Derived Mesenchymal Stem Cells" in Frontiers in Veterinary Science, 8 (2021),
https://doi.org/10.3389/fvets.2021.732073 . .
1
4
2

The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls

Mihaljević, Marina; Franić, Dusanka; Soldatović, Ivan; Lukić, Iva; Andrić-Petrović, Sanja; Mirjanić, Tijana; Stanković, Biljana; Zukić, Branka; Zeljić, Katarina; Gašić, Vladimir; Novaković, Ivana; Pavlović, Sonja; Adžić, Miroslav; Marić, Nadja P.

(Pergamon-Elsevier Science Ltd, Oxford, 2021)

TY  - JOUR
AU  - Mihaljević, Marina
AU  - Franić, Dusanka
AU  - Soldatović, Ivan
AU  - Lukić, Iva
AU  - Andrić-Petrović, Sanja
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Zeljić, Katarina
AU  - Gašić, Vladimir
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
AU  - Marić, Nadja P.
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1451
AB  - Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Psychoneuroendocrinology
T1  - The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
VL  - 128
DO  - 10.1016/j.psyneuen.2021.105205
ER  - 
@article{
author = "Mihaljević, Marina and Franić, Dusanka and Soldatović, Ivan and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Zukić, Branka and Zeljić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nadja P.",
year = "2021",
abstract = "Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Psychoneuroendocrinology",
title = "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls",
volume = "128",
doi = "10.1016/j.psyneuen.2021.105205"
}
Mihaljević, M., Franić, D., Soldatović, I., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Zukić, B., Zeljić, K., Gašić, V., Novaković, I., Pavlović, S., Adžić, M.,& Marić, N. P.. (2021). The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology
Pergamon-Elsevier Science Ltd, Oxford., 128.
https://doi.org/10.1016/j.psyneuen.2021.105205
Mihaljević M, Franić D, Soldatović I, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Zukić B, Zeljić K, Gašić V, Novaković I, Pavlović S, Adžić M, Marić NP. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology. 2021;128.
doi:10.1016/j.psyneuen.2021.105205 .
Mihaljević, Marina, Franić, Dusanka, Soldatović, Ivan, Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Zukić, Branka, Zeljić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nadja P., "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls" in Psychoneuroendocrinology, 128 (2021),
https://doi.org/10.1016/j.psyneuen.2021.105205 . .
2
7
2
6

Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients

Vuković, Vojin; Karan-Đurašević, Teodora; Antić, Darko; Tošić, Nataša; Kostić, Tatjana; Marjanović, Irena; Denčić-Fekete, Marija; Đurašinović, Vladislava; Pavlović, Sonja; Mihaljević, Biljana

(Frontiers Media Sa, Lausanne, 2020)

TY  - JOUR
AU  - Vuković, Vojin
AU  - Karan-Đurašević, Teodora
AU  - Antić, Darko
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Marjanović, Irena
AU  - Denčić-Fekete, Marija
AU  - Đurašinović, Vladislava
AU  - Pavlović, Sonja
AU  - Mihaljević, Biljana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1321
AB  - Fludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high-expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients.
PB  - Frontiers Media Sa, Lausanne
T2  - Pathology & Oncology Research
T1  - Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients
EP  - 752
IS  - 2
SP  - 743
VL  - 26
DO  - 10.1007/s12253-019-00613-4
ER  - 
@article{
author = "Vuković, Vojin and Karan-Đurašević, Teodora and Antić, Darko and Tošić, Nataša and Kostić, Tatjana and Marjanović, Irena and Denčić-Fekete, Marija and Đurašinović, Vladislava and Pavlović, Sonja and Mihaljević, Biljana",
year = "2020",
abstract = "Fludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high-expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Pathology & Oncology Research",
title = "Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients",
pages = "752-743",
number = "2",
volume = "26",
doi = "10.1007/s12253-019-00613-4"
}
Vuković, V., Karan-Đurašević, T., Antić, D., Tošić, N., Kostić, T., Marjanović, I., Denčić-Fekete, M., Đurašinović, V., Pavlović, S.,& Mihaljević, B.. (2020). Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients. in Pathology & Oncology Research
Frontiers Media Sa, Lausanne., 26(2), 743-752.
https://doi.org/10.1007/s12253-019-00613-4
Vuković V, Karan-Đurašević T, Antić D, Tošić N, Kostić T, Marjanović I, Denčić-Fekete M, Đurašinović V, Pavlović S, Mihaljević B. Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients. in Pathology & Oncology Research. 2020;26(2):743-752.
doi:10.1007/s12253-019-00613-4 .
Vuković, Vojin, Karan-Đurašević, Teodora, Antić, Darko, Tošić, Nataša, Kostić, Tatjana, Marjanović, Irena, Denčić-Fekete, Marija, Đurašinović, Vladislava, Pavlović, Sonja, Mihaljević, Biljana, "Association of SLC28A3 Gene Expression and CYP2B6*6 Allele with the Response to Fludarabine Plus Cyclophosphamide in Chronic Lymphocytic Leukemia Patients" in Pathology & Oncology Research, 26, no. 2 (2020):743-752,
https://doi.org/10.1007/s12253-019-00613-4 . .
2
1
2

Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype

Marjanović, Irena; Karan-Đurašević, Teodora; Kostić, Tatjana; Virijević, Marijana; Suvajdžić-Vuković, Nada; Pavlović, Sonja; Tošić, Nataša

(Springer India, New Delhi, 2020)

TY  - JOUR
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1391
AB  - According to current criteria, patients with acute myeloid leukemia with normal karyotype (AML-NK) are classified as intermediate risk patients. There is a constant need for additional molecular markers that will help in substratification into more precise prognostic groups. One of the potential new markers is Ecotropic viral integration 1 site (EVI1) transcriptional factor, whose expression is dissregulated in abnormal hematopoietic process. The purpose of this study was to examine EVI1 gene expression in 104 adult AML-NK patients and on 10 healthy bone marrow donors using real-time polymerase chain reaction method, and to evaluate association between EVI1 expression level and other molecular and clinical features, and to examine its potential influence on the prognosis of the disease. Overexpression of EVI1 gene (EVI1(+) status) was present in 17% of patients. Increased EVI1 expression was predominantly found in patients with lower WBC count (P = 0.003) and lower bone marrow blast percentage (P = 0.005). EVI1(+) patients had lower WT1 expression level (P = 0.041), and were negative for FLT3-ITD and NPM1 mutations (P = 0.036 and P = 0.003). Patients with EVI1(+) status had higher complete remission rate (P = 0.047), but EVI1 expression didn't influence overall and disease free survival. EVI1 expression status alone, cannot be used as a new marker for more precise substratification of AML-NK patients. Further investigations conducted on larger number of patients may indicate how EVI1 expression could influence the prognosis and outcome of AML-NK patients, by itself, or in the context of other molecular and clinical parameters.
PB  - Springer India, New Delhi
T2  - Indian Journal of Hematology and Blood Transfusion
T1  - Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype
EP  - 299
IS  - 2
SP  - 292
VL  - 36
DO  - 10.1007/s12288-019-01227-1
ER  - 
@article{
author = "Marjanović, Irena and Karan-Đurašević, Teodora and Kostić, Tatjana and Virijević, Marijana and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "According to current criteria, patients with acute myeloid leukemia with normal karyotype (AML-NK) are classified as intermediate risk patients. There is a constant need for additional molecular markers that will help in substratification into more precise prognostic groups. One of the potential new markers is Ecotropic viral integration 1 site (EVI1) transcriptional factor, whose expression is dissregulated in abnormal hematopoietic process. The purpose of this study was to examine EVI1 gene expression in 104 adult AML-NK patients and on 10 healthy bone marrow donors using real-time polymerase chain reaction method, and to evaluate association between EVI1 expression level and other molecular and clinical features, and to examine its potential influence on the prognosis of the disease. Overexpression of EVI1 gene (EVI1(+) status) was present in 17% of patients. Increased EVI1 expression was predominantly found in patients with lower WBC count (P = 0.003) and lower bone marrow blast percentage (P = 0.005). EVI1(+) patients had lower WT1 expression level (P = 0.041), and were negative for FLT3-ITD and NPM1 mutations (P = 0.036 and P = 0.003). Patients with EVI1(+) status had higher complete remission rate (P = 0.047), but EVI1 expression didn't influence overall and disease free survival. EVI1 expression status alone, cannot be used as a new marker for more precise substratification of AML-NK patients. Further investigations conducted on larger number of patients may indicate how EVI1 expression could influence the prognosis and outcome of AML-NK patients, by itself, or in the context of other molecular and clinical parameters.",
publisher = "Springer India, New Delhi",
journal = "Indian Journal of Hematology and Blood Transfusion",
title = "Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype",
pages = "299-292",
number = "2",
volume = "36",
doi = "10.1007/s12288-019-01227-1"
}
Marjanović, I., Karan-Đurašević, T., Kostić, T., Virijević, M., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype. in Indian Journal of Hematology and Blood Transfusion
Springer India, New Delhi., 36(2), 292-299.
https://doi.org/10.1007/s12288-019-01227-1
Marjanović I, Karan-Đurašević T, Kostić T, Virijević M, Suvajdžić-Vuković N, Pavlović S, Tošić N. Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype. in Indian Journal of Hematology and Blood Transfusion. 2020;36(2):292-299.
doi:10.1007/s12288-019-01227-1 .
Marjanović, Irena, Karan-Đurašević, Teodora, Kostić, Tatjana, Virijević, Marijana, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "Expression Pattern and Prognostic Significance of EVI1 Gene in Adult Acute Myeloid Leukemia Patients with Normal Karyotype" in Indian Journal of Hematology and Blood Transfusion, 36, no. 2 (2020):292-299,
https://doi.org/10.1007/s12288-019-01227-1 . .
1
7
4
6

Varijante kodirajućih i nekodirajućih regiona gena uzročnika dijabetesa adultnog tipa kod mladih kao modulatori fenotipa i regulatori genske ekspresije

Komazec, Jovana

(Univerzitet u Beogradu, Biološki fakultet, 2020)

TY  - THES
AU  - Komazec, Jovana
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=8066
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:23529/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=35616265
UR  - https://nardus.mpn.gov.rs/handle/123456789/18218
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/61
AB  - Dijabetes adultnog tipa kod mladih (MODY) je nasledni, autozomno dominantni oblik dijabetesa, klinički i genetički veoma heterogen, koji nastaje kao posledica primarne disfunkcije β-ćelija pankreasa. MODY nastaje usled genetičkih varijanti u jednom od brojnih gena asociranih sa MODY dijabetesom, te je metodom sekvenciranja nove generacije i metodom istovremenog umnožavanja vezanih proba, prvi put u Srbij, analizirano 13 gena uzročnika MODY dijabetesa kod 29 klinički suspektnih pedijatrijskih pacijenata. Kombinovanjem ove dve metode detektovano je 20 različitih varijanti kod 75,9% pacijenata u 4 različita gena. Varijante u dva gena, GCK i HNF1B, detekotvane redom, kod 50% i 22,7% pacijenata, predstavljale su glavne uzročnike MODY dijabetesa u ovoj grupi pacijenata. U ovoj studiji identifikovana je i jedna nova prethodno neprijavljena varijanta u GCK genu, c.596T>C; p.Val199Ala, za koju su in silico predikcije nedvosmisleno pokazale da je patogena. Kako bi se detektovale varijante u promotorskom regionu, koje takođe dovode do MODY dijabetesa, analizirani su promotorski regioni četiri najčešća gena uzročnika MODY dijabetesa. Varijantni set u promotrskom regionu GCK gena (−282C>T; −194A>G; 402C>G) i varijanta c.-154-160insTGGGGGT u promotoru HNF1A gena, odabrane su kako bi se u funkcionalnim esejima u ćelijskoj kulturi ispitao njihov uticaj na ekspresiju datih gena. Analizirane su i interakcije ovih potencijalnih regulatornih elemenata sa transkripcionim faktorima u esejima usporene elektroforetske pokretljivosti. Rezultati funkcionalne analize odabarnih promotorskih varijanti ukazali su da varijante u promotoru, osim potencijalno patogenog efekta, mogu da imaju i ulogu modifikatora fenotipa, čime su dopunjena postojeća znanja o varijantama u promotorima MODY gena.
AB  - Maturity-onset diabetes of the young (MODY) is an inherited, autosomal dominant form of diabetes, clinically and genetically very heterogeneous, resulting from primary β-cell dysfunction. Since MODY diabetes is caused by single gene variants in one of the many MODY-related genes, next generation sequencing and multiplex ligation-dependent probe amplification analysis were used to analyze 13 MODY-relate genes in 29 clinically suspected pediatric patients, for the first time in Serbia. Combining these two methods, 20 different variants, found in 4 genes, were identified in 75.9% patients. Variants in the GCK and HNF1B gene, detected in 50% and 22.7% patients, respectively, were the main cause of MODY diabetes in our patients. Also, a novel variant in the GCK gene: c.596T>C, p.Val199Ala was identified and predicted to be pathogenic by in silico algorithms. Due to the fact that promoter variants can also lead to MODY diabetes, promoter regions of the four most common MODY genes were screened. Two variants, the variant set in the promoter region of the GCK gene (−282C>T; −194A>G; 402C>G), and the variant c.-154-160insTGGGGGT in the promoter of the HNF1A gene, were selected to analyze their effect on gene expression in functional cell culture studies. Also, electrophoretic mobility shift assay was carried out to investigate the interaction of potential transcription factors with the promoter region surrounding the variant, as well as whether the variants affect the binding of those transcription factors. The results of the functional analysis of the selected promoter variants indicated that variants in the promoter, in addition to potentially pathogenic effect, may also play the role of a phenotype modifier, thus supplementing the existing knowledge about variants in the promoters of MODY genes.
PB  - Univerzitet u Beogradu, Biološki fakultet
T1  - Varijante kodirajućih i nekodirajućih regiona gena uzročnika dijabetesa adultnog tipa kod mladih kao modulatori fenotipa i regulatori genske ekspresije
T1  - Coding and noncoding variants of disease-causing genes of maturity-onset diabetes of the young: phenotype modulators and regulators of gene expression
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18218
ER  - 
@phdthesis{
author = "Komazec, Jovana",
year = "2020",
abstract = "Dijabetes adultnog tipa kod mladih (MODY) je nasledni, autozomno dominantni oblik dijabetesa, klinički i genetički veoma heterogen, koji nastaje kao posledica primarne disfunkcije β-ćelija pankreasa. MODY nastaje usled genetičkih varijanti u jednom od brojnih gena asociranih sa MODY dijabetesom, te je metodom sekvenciranja nove generacije i metodom istovremenog umnožavanja vezanih proba, prvi put u Srbij, analizirano 13 gena uzročnika MODY dijabetesa kod 29 klinički suspektnih pedijatrijskih pacijenata. Kombinovanjem ove dve metode detektovano je 20 različitih varijanti kod 75,9% pacijenata u 4 različita gena. Varijante u dva gena, GCK i HNF1B, detekotvane redom, kod 50% i 22,7% pacijenata, predstavljale su glavne uzročnike MODY dijabetesa u ovoj grupi pacijenata. U ovoj studiji identifikovana je i jedna nova prethodno neprijavljena varijanta u GCK genu, c.596T>C; p.Val199Ala, za koju su in silico predikcije nedvosmisleno pokazale da je patogena. Kako bi se detektovale varijante u promotorskom regionu, koje takođe dovode do MODY dijabetesa, analizirani su promotorski regioni četiri najčešća gena uzročnika MODY dijabetesa. Varijantni set u promotrskom regionu GCK gena (−282C>T; −194A>G; 402C>G) i varijanta c.-154-160insTGGGGGT u promotoru HNF1A gena, odabrane su kako bi se u funkcionalnim esejima u ćelijskoj kulturi ispitao njihov uticaj na ekspresiju datih gena. Analizirane su i interakcije ovih potencijalnih regulatornih elemenata sa transkripcionim faktorima u esejima usporene elektroforetske pokretljivosti. Rezultati funkcionalne analize odabarnih promotorskih varijanti ukazali su da varijante u promotoru, osim potencijalno patogenog efekta, mogu da imaju i ulogu modifikatora fenotipa, čime su dopunjena postojeća znanja o varijantama u promotorima MODY gena., Maturity-onset diabetes of the young (MODY) is an inherited, autosomal dominant form of diabetes, clinically and genetically very heterogeneous, resulting from primary β-cell dysfunction. Since MODY diabetes is caused by single gene variants in one of the many MODY-related genes, next generation sequencing and multiplex ligation-dependent probe amplification analysis were used to analyze 13 MODY-relate genes in 29 clinically suspected pediatric patients, for the first time in Serbia. Combining these two methods, 20 different variants, found in 4 genes, were identified in 75.9% patients. Variants in the GCK and HNF1B gene, detected in 50% and 22.7% patients, respectively, were the main cause of MODY diabetes in our patients. Also, a novel variant in the GCK gene: c.596T>C, p.Val199Ala was identified and predicted to be pathogenic by in silico algorithms. Due to the fact that promoter variants can also lead to MODY diabetes, promoter regions of the four most common MODY genes were screened. Two variants, the variant set in the promoter region of the GCK gene (−282C>T; −194A>G; 402C>G), and the variant c.-154-160insTGGGGGT in the promoter of the HNF1A gene, were selected to analyze their effect on gene expression in functional cell culture studies. Also, electrophoretic mobility shift assay was carried out to investigate the interaction of potential transcription factors with the promoter region surrounding the variant, as well as whether the variants affect the binding of those transcription factors. The results of the functional analysis of the selected promoter variants indicated that variants in the promoter, in addition to potentially pathogenic effect, may also play the role of a phenotype modifier, thus supplementing the existing knowledge about variants in the promoters of MODY genes.",
publisher = "Univerzitet u Beogradu, Biološki fakultet",
title = "Varijante kodirajućih i nekodirajućih regiona gena uzročnika dijabetesa adultnog tipa kod mladih kao modulatori fenotipa i regulatori genske ekspresije, Coding and noncoding variants of disease-causing genes of maturity-onset diabetes of the young: phenotype modulators and regulators of gene expression",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18218"
}
Komazec, J.. (2020). Varijante kodirajućih i nekodirajućih regiona gena uzročnika dijabetesa adultnog tipa kod mladih kao modulatori fenotipa i regulatori genske ekspresije. 
Univerzitet u Beogradu, Biološki fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_18218
Komazec J. Varijante kodirajućih i nekodirajućih regiona gena uzročnika dijabetesa adultnog tipa kod mladih kao modulatori fenotipa i regulatori genske ekspresije. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_18218 .
Komazec, Jovana, "Varijante kodirajućih i nekodirajućih regiona gena uzročnika dijabetesa adultnog tipa kod mladih kao modulatori fenotipa i regulatori genske ekspresije" (2020),
https://hdl.handle.net/21.15107/rcub_nardus_18218 .

Genomic profiling of thymoma using a targeted high-throughput approach

Perić, Jelena; Samaradzic, Natalija; Trifunovic, Vesna Skodric; Tošić, Nataša ; Stojsic, Jelena; Pavlović, Sonja; Jovanovic, Dragana

(2020)

TY  - JOUR
AU  - Perić, Jelena
AU  - Samaradzic, Natalija
AU  - Trifunovic, Vesna Skodric
AU  - Tošić, Nataša 
AU  - Stojsic, Jelena
AU  - Pavlović, Sonja
AU  - Jovanovic, Dragana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1643
AB  - Introduction:  Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology.   Material and methods:  Genomic...
T2  - Archives of Medical Science
T2  - Archives of Medical ScienceArch Med Sci
T1  - Genomic profiling of thymoma using a targeted high-throughput approach
DO  - 10.5114/aoms.2020.96537
ER  - 
@article{
author = "Perić, Jelena and Samaradzic, Natalija and Trifunovic, Vesna Skodric and Tošić, Nataša  and Stojsic, Jelena and Pavlović, Sonja and Jovanovic, Dragana",
year = "2020",
abstract = "Introduction:  Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology.   Material and methods:  Genomic...",
journal = "Archives of Medical Science, Archives of Medical ScienceArch Med Sci",
title = "Genomic profiling of thymoma using a targeted high-throughput approach",
doi = "10.5114/aoms.2020.96537"
}
Perić, J., Samaradzic, N., Trifunovic, V. S., Tošić, N., Stojsic, J., Pavlović, S.,& Jovanovic, D.. (2020). Genomic profiling of thymoma using a targeted high-throughput approach. in Archives of Medical Science.
https://doi.org/10.5114/aoms.2020.96537
Perić J, Samaradzic N, Trifunovic VS, Tošić N, Stojsic J, Pavlović S, Jovanovic D. Genomic profiling of thymoma using a targeted high-throughput approach. in Archives of Medical Science. 2020;.
doi:10.5114/aoms.2020.96537 .
Perić, Jelena, Samaradzic, Natalija, Trifunovic, Vesna Skodric, Tošić, Nataša , Stojsic, Jelena, Pavlović, Sonja, Jovanovic, Dragana, "Genomic profiling of thymoma using a targeted high-throughput approach" in Archives of Medical Science (2020),
https://doi.org/10.5114/aoms.2020.96537 . .
4

Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem

Đorđević, Vesna; Tošić, Nataša; Denčić-Fekete, Marija; Virijević, Marijana; Jovanović, Jelica; Jaković, Ljubomir; Kraguljac-Kurtović, Nada; Bogdanović, Andrija; Kostić, Tatjana; Pavlović, Sonja

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2020)

TY  - JOUR
AU  - Đorđević, Vesna
AU  - Tošić, Nataša
AU  - Denčić-Fekete, Marija
AU  - Virijević, Marijana
AU  - Jovanović, Jelica
AU  - Jaković, Ljubomir
AU  - Kraguljac-Kurtović, Nada
AU  - Bogdanović, Andrija
AU  - Kostić, Tatjana
AU  - Pavlović, Sonja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1371
AB  - Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja.
AB  - Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem
T1  - Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing
EP  - 102
IS  - 1
SP  - 97
VL  - 77
DO  - 10.2298/VSP170620040D
ER  - 
@article{
author = "Đorđević, Vesna and Tošić, Nataša and Denčić-Fekete, Marija and Virijević, Marijana and Jovanović, Jelica and Jaković, Ljubomir and Kraguljac-Kurtović, Nada and Bogdanović, Andrija and Kostić, Tatjana and Pavlović, Sonja",
year = "2020",
abstract = "Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja., Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem, Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing",
pages = "102-97",
number = "1",
volume = "77",
doi = "10.2298/VSP170620040D"
}
Đorđević, V., Tošić, N., Denčić-Fekete, M., Virijević, M., Jovanović, J., Jaković, L., Kraguljac-Kurtović, N., Bogdanović, A., Kostić, T.,& Pavlović, S.. (2020). Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 77(1), 97-102.
https://doi.org/10.2298/VSP170620040D
Đorđević V, Tošić N, Denčić-Fekete M, Virijević M, Jovanović J, Jaković L, Kraguljac-Kurtović N, Bogdanović A, Kostić T, Pavlović S. Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled. 2020;77(1):97-102.
doi:10.2298/VSP170620040D .
Đorđević, Vesna, Tošić, Nataša, Denčić-Fekete, Marija, Virijević, Marijana, Jovanović, Jelica, Jaković, Ljubomir, Kraguljac-Kurtović, Nada, Bogdanović, Andrija, Kostić, Tatjana, Pavlović, Sonja, "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem" in Vojnosanitetski pregled, 77, no. 1 (2020):97-102,
https://doi.org/10.2298/VSP170620040D . .
1
1
1

Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells

Nikčević, Gordana; Srzentić Dražilov, Sanja; Karan-Đurašević, Teodora; Tošić, Nataša; Kontos, Christos K.; Scorilas, Andreas; Pavlović, Sonja

(Elsevier, Amsterdam, 2020)

TY  - JOUR
AU  - Nikčević, Gordana
AU  - Srzentić Dražilov, Sanja
AU  - Karan-Đurašević, Teodora
AU  - Tošić, Nataša
AU  - Kontos, Christos K.
AU  - Scorilas, Andreas
AU  - Pavlović, Sonja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1326
AB  - The BCL2L12, one of the latest discovered members of the BCL2 family, has both pro- and anti-apoptotic roles that are cell-type-dependent. Its role in tumorigenesis is highly implicated. Sixty-three splice variants of this gene have been identified so far, with significant differences in expression patterns between various cancer cell lines. Presently, little is known regarding the regulation of expression of the BCL2L12 gene. For the vast majority of BCL2L12 gene splice variants, the 5'- and 3'-untranslated regions as well as their transcriptional regulation have not been determined yet. The aim of this study was to get insight into the regulation of the BCL2L12 gene transcription in human chronic myelogenous leukemia (K562) cell line. Our results point to the activity of novel transcription start site of the BCL2L12 gene and indicate that Sp1 and GATA-1 transcription factors could be involved in the regulation of BCL2L12 gene expression in K562 cells. The previously reported active promoter of BCL2L12 gene differs from the one we described in our study. If this novel BCL2L12 promoter is confirmed to be active in other malignancies, transcripts generated from this region could be considered as new cancer-specific biomarkers. The results of our study contribute to the better understanding of the transcriptional regulation of the BCL2L12 gene.
PB  - Elsevier, Amsterdam
T2  - Gene
T1  - Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells
VL  - 750
DO  - 10.1016/j.gene.2020.144723
ER  - 
@article{
author = "Nikčević, Gordana and Srzentić Dražilov, Sanja and Karan-Đurašević, Teodora and Tošić, Nataša and Kontos, Christos K. and Scorilas, Andreas and Pavlović, Sonja",
year = "2020",
abstract = "The BCL2L12, one of the latest discovered members of the BCL2 family, has both pro- and anti-apoptotic roles that are cell-type-dependent. Its role in tumorigenesis is highly implicated. Sixty-three splice variants of this gene have been identified so far, with significant differences in expression patterns between various cancer cell lines. Presently, little is known regarding the regulation of expression of the BCL2L12 gene. For the vast majority of BCL2L12 gene splice variants, the 5'- and 3'-untranslated regions as well as their transcriptional regulation have not been determined yet. The aim of this study was to get insight into the regulation of the BCL2L12 gene transcription in human chronic myelogenous leukemia (K562) cell line. Our results point to the activity of novel transcription start site of the BCL2L12 gene and indicate that Sp1 and GATA-1 transcription factors could be involved in the regulation of BCL2L12 gene expression in K562 cells. The previously reported active promoter of BCL2L12 gene differs from the one we described in our study. If this novel BCL2L12 promoter is confirmed to be active in other malignancies, transcripts generated from this region could be considered as new cancer-specific biomarkers. The results of our study contribute to the better understanding of the transcriptional regulation of the BCL2L12 gene.",
publisher = "Elsevier, Amsterdam",
journal = "Gene",
title = "Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells",
volume = "750",
doi = "10.1016/j.gene.2020.144723"
}
Nikčević, G., Srzentić Dražilov, S., Karan-Đurašević, T., Tošić, N., Kontos, C. K., Scorilas, A.,& Pavlović, S.. (2020). Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells. in Gene
Elsevier, Amsterdam., 750.
https://doi.org/10.1016/j.gene.2020.144723
Nikčević G, Srzentić Dražilov S, Karan-Đurašević T, Tošić N, Kontos CK, Scorilas A, Pavlović S. Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells. in Gene. 2020;750.
doi:10.1016/j.gene.2020.144723 .
Nikčević, Gordana, Srzentić Dražilov, Sanja, Karan-Đurašević, Teodora, Tošić, Nataša, Kontos, Christos K., Scorilas, Andreas, Pavlović, Sonja, "Complex transcriptional regulation of the BCL2L12 gene: Novel, active promoter in K562 cells" in Gene, 750 (2020),
https://doi.org/10.1016/j.gene.2020.144723 . .
4
4

The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients

Mitrović, Mirjana; Kostić, Tatjana; Virijević, Marijana; Karan-Đurašević, Teodora; Suvajdžić-Vuković, Nada; Pavlović, Sonja; Tošić, Nataša

(Wiley, Hoboken, 2020)

TY  - JOUR
AU  - Mitrović, Mirjana
AU  - Kostić, Tatjana
AU  - Virijević, Marijana
AU  - Karan-Đurašević, Teodora
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1403
AB  - Introduction Patients with acute promyelocytic leukemia (APL) are characterized by the highest expression of Wilms' tumor 1 (WT1) gene compared with other subtypes of acute myeloid leukemia, and yet this molecular marker is almost never used for risk stratification and in therapy response monitoring. Methods Quantitative assessment of Wilms' tumor 1 (WT1) gene transcripts was performed using real-time PCR method. The bone marrow samples were collected at the time of diagnosis for 47 APL patients, and for 31/47 patients during follow-up/relapse of the disease (129 samples in total). We examined how this molecular marker can be used for prognosis and minimal residual disease (MRD) monitoring. Results Increased WT1 expression was found in 34% of patients. WT1(high) status was an independent unfavorable factor for early death occurrence and was associated with shorter overall survival (OS). Assessment of log reduction value of WT1 expression in paired diagnosis/complete remission samples did not reveal its impact on relapse rate, disease-free survival, and OS. Also, measurement of WT1 expression level at different time points during therapy was not a reliable method for MRD monitoring. Conclusion Increased expression of WT1 gene detected in high proportion of APL patients could be considered as a marker for more precise risk stratification models in an attempt to further improve treatment and outcome of APL patients.
PB  - Wiley, Hoboken
T2  - International Journal of Laboratory Hematology
T1  - The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients
EP  - 87
IS  - 1
SP  - 82
VL  - 42
DO  - 10.1111/ijlh.13144
ER  - 
@article{
author = "Mitrović, Mirjana and Kostić, Tatjana and Virijević, Marijana and Karan-Đurašević, Teodora and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Tošić, Nataša",
year = "2020",
abstract = "Introduction Patients with acute promyelocytic leukemia (APL) are characterized by the highest expression of Wilms' tumor 1 (WT1) gene compared with other subtypes of acute myeloid leukemia, and yet this molecular marker is almost never used for risk stratification and in therapy response monitoring. Methods Quantitative assessment of Wilms' tumor 1 (WT1) gene transcripts was performed using real-time PCR method. The bone marrow samples were collected at the time of diagnosis for 47 APL patients, and for 31/47 patients during follow-up/relapse of the disease (129 samples in total). We examined how this molecular marker can be used for prognosis and minimal residual disease (MRD) monitoring. Results Increased WT1 expression was found in 34% of patients. WT1(high) status was an independent unfavorable factor for early death occurrence and was associated with shorter overall survival (OS). Assessment of log reduction value of WT1 expression in paired diagnosis/complete remission samples did not reveal its impact on relapse rate, disease-free survival, and OS. Also, measurement of WT1 expression level at different time points during therapy was not a reliable method for MRD monitoring. Conclusion Increased expression of WT1 gene detected in high proportion of APL patients could be considered as a marker for more precise risk stratification models in an attempt to further improve treatment and outcome of APL patients.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Laboratory Hematology",
title = "The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients",
pages = "87-82",
number = "1",
volume = "42",
doi = "10.1111/ijlh.13144"
}
Mitrović, M., Kostić, T., Virijević, M., Karan-Đurašević, T., Suvajdžić-Vuković, N., Pavlović, S.,& Tošić, N.. (2020). The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients. in International Journal of Laboratory Hematology
Wiley, Hoboken., 42(1), 82-87.
https://doi.org/10.1111/ijlh.13144
Mitrović M, Kostić T, Virijević M, Karan-Đurašević T, Suvajdžić-Vuković N, Pavlović S, Tošić N. The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients. in International Journal of Laboratory Hematology. 2020;42(1):82-87.
doi:10.1111/ijlh.13144 .
Mitrović, Mirjana, Kostić, Tatjana, Virijević, Marijana, Karan-Đurašević, Teodora, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Tošić, Nataša, "The influence of Wilms' tumor 1 gene expression level on prognosis and risk stratification of acute promyelocytic leukemia patients" in International Journal of Laboratory Hematology, 42, no. 1 (2020):82-87,
https://doi.org/10.1111/ijlh.13144 . .
1
9
2
7

Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib

Sarajlija, Adrijan; Đorđević, Maja; Kecman, Bozica; Skakić, Anita; Pavlović, Sonja; Pasić, Srdjan; Stojiljković, Maja

(Elsevier, Amsterdam, 2020)

TY  - JOUR
AU  - Sarajlija, Adrijan
AU  - Đorđević, Maja
AU  - Kecman, Bozica
AU  - Skakić, Anita
AU  - Pavlović, Sonja
AU  - Pasić, Srdjan
AU  - Stojiljković, Maja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1387
AB  - Background: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. Methods: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. Results: Absolute neutrophil count (ANC)  lt  1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC  lt  500/mm(3)) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T  gt  A/c.785G  gt  A and c.81T  gt  A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G  gt  A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. Conclusions: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI.
PB  - Elsevier, Amsterdam
T2  - European Journal of Medical Genetics
T1  - Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib
IS  - 3
VL  - 63
DO  - 10.1016/j.ejmg.2019.103767
ER  - 
@article{
author = "Sarajlija, Adrijan and Đorđević, Maja and Kecman, Bozica and Skakić, Anita and Pavlović, Sonja and Pasić, Srdjan and Stojiljković, Maja",
year = "2020",
abstract = "Background: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. Methods: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. Results: Absolute neutrophil count (ANC)  lt  1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC  lt  500/mm(3)) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T  gt  A/c.785G  gt  A and c.81T  gt  A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G  gt  A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. Conclusions: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI.",
publisher = "Elsevier, Amsterdam",
journal = "European Journal of Medical Genetics",
title = "Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib",
number = "3",
volume = "63",
doi = "10.1016/j.ejmg.2019.103767"
}
Sarajlija, A., Đorđević, M., Kecman, B., Skakić, A., Pavlović, S., Pasić, S.,& Stojiljković, M.. (2020). Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib. in European Journal of Medical Genetics
Elsevier, Amsterdam., 63(3).
https://doi.org/10.1016/j.ejmg.2019.103767
Sarajlija A, Đorđević M, Kecman B, Skakić A, Pavlović S, Pasić S, Stojiljković M. Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib. in European Journal of Medical Genetics. 2020;63(3).
doi:10.1016/j.ejmg.2019.103767 .
Sarajlija, Adrijan, Đorđević, Maja, Kecman, Bozica, Skakić, Anita, Pavlović, Sonja, Pasić, Srdjan, Stojiljković, Maja, "Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib" in European Journal of Medical Genetics, 63, no. 3 (2020),
https://doi.org/10.1016/j.ejmg.2019.103767 . .
10
1
9

Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation

Dragasević, Sanja; Stanković, Biljana; Kotur, Nikola; Sokić-Milutinović, Aleksandra; Milovanović, Tamara; Lukić, Snežana; Milosavljević, Tomica; Srzentić Dražilov, Sanja; Klaassen, Kristel; Pavlović, Sonja; Popović, Dragan

(Mary Ann Liebert, Inc, New Rochelle, 2020)

TY  - JOUR
AU  - Dragasević, Sanja
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Sokić-Milutinović, Aleksandra
AU  - Milovanović, Tamara
AU  - Lukić, Snežana
AU  - Milosavljević, Tomica
AU  - Srzentić Dražilov, Sanja
AU  - Klaassen, Kristel
AU  - Pavlović, Sonja
AU  - Popović, Dragan
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1398
AB  - Background: This study analyzed poorly understood relationship of two overlapping conditions: metabolic syndrome (MeS) and inflammatory bowel disease (IBD), both associated with inflammation in the visceral adipose tissue. Methods: Newly diagnosed 104 IBD patients, of which 50 Crohn's disease (CD) and 54 ulcerative colitis (UC), and 45 non-IBD controls were examined for MeS-related obesity and lipid markers. Th-17 immune genes IL17A, IL17F, IL23A, and TLR9 mRNAs were measured in intestinal mucosa by qRT-PCR. Subjects were genotyped for obesity-associated FTO variant rs9939609 by polymerase chain reaction-amplification refractory mutation system. Results: CD was associated with MeS (P = 0.01), while both CD and UC were associated with central obesity (P = 10(-5), P = 0.002, respectively) and low levels of high-density lipoprotein (HDL) cholesterol (P = 5 x 10(-6), P = 6 x 10(-6), respectively). IBD lipid profile was characterized by decreased total and HDL cholesterol, while low-density lipoprotein cholesterol was reduced only in CD. Negative correlations were found between total cholesterol and CD activity index (P = 0.005), waist circumference and IL17A as well as IL17F mRNA levels in inflamed CD colon (P = 0.003, P = 0.001, respectively). Carriers of FTO rs9939609 AA genotype showed increased risk of CD (OR 2.6, P = 0.01). Conclusions: MeS, central obesity, and dyslipidemia could be important for IBD pathogenesis. This could influence therapeutic approaches and prevention strategies in high-risk groups.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Metabolic Syndrome and Related Disorders
T1  - Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation
EP  - 38
IS  - 1
SP  - 31
VL  - 18
DO  - 10.1089/met.2019.0090
ER  - 
@article{
author = "Dragasević, Sanja and Stanković, Biljana and Kotur, Nikola and Sokić-Milutinović, Aleksandra and Milovanović, Tamara and Lukić, Snežana and Milosavljević, Tomica and Srzentić Dražilov, Sanja and Klaassen, Kristel and Pavlović, Sonja and Popović, Dragan",
year = "2020",
abstract = "Background: This study analyzed poorly understood relationship of two overlapping conditions: metabolic syndrome (MeS) and inflammatory bowel disease (IBD), both associated with inflammation in the visceral adipose tissue. Methods: Newly diagnosed 104 IBD patients, of which 50 Crohn's disease (CD) and 54 ulcerative colitis (UC), and 45 non-IBD controls were examined for MeS-related obesity and lipid markers. Th-17 immune genes IL17A, IL17F, IL23A, and TLR9 mRNAs were measured in intestinal mucosa by qRT-PCR. Subjects were genotyped for obesity-associated FTO variant rs9939609 by polymerase chain reaction-amplification refractory mutation system. Results: CD was associated with MeS (P = 0.01), while both CD and UC were associated with central obesity (P = 10(-5), P = 0.002, respectively) and low levels of high-density lipoprotein (HDL) cholesterol (P = 5 x 10(-6), P = 6 x 10(-6), respectively). IBD lipid profile was characterized by decreased total and HDL cholesterol, while low-density lipoprotein cholesterol was reduced only in CD. Negative correlations were found between total cholesterol and CD activity index (P = 0.005), waist circumference and IL17A as well as IL17F mRNA levels in inflamed CD colon (P = 0.003, P = 0.001, respectively). Carriers of FTO rs9939609 AA genotype showed increased risk of CD (OR 2.6, P = 0.01). Conclusions: MeS, central obesity, and dyslipidemia could be important for IBD pathogenesis. This could influence therapeutic approaches and prevention strategies in high-risk groups.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Metabolic Syndrome and Related Disorders",
title = "Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation",
pages = "38-31",
number = "1",
volume = "18",
doi = "10.1089/met.2019.0090"
}
Dragasević, S., Stanković, B., Kotur, N., Sokić-Milutinović, A., Milovanović, T., Lukić, S., Milosavljević, T., Srzentić Dražilov, S., Klaassen, K., Pavlović, S.,& Popović, D.. (2020). Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation. in Metabolic Syndrome and Related Disorders
Mary Ann Liebert, Inc, New Rochelle., 18(1), 31-38.
https://doi.org/10.1089/met.2019.0090
Dragasević S, Stanković B, Kotur N, Sokić-Milutinović A, Milovanović T, Lukić S, Milosavljević T, Srzentić Dražilov S, Klaassen K, Pavlović S, Popović D. Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation. in Metabolic Syndrome and Related Disorders. 2020;18(1):31-38.
doi:10.1089/met.2019.0090 .
Dragasević, Sanja, Stanković, Biljana, Kotur, Nikola, Sokić-Milutinović, Aleksandra, Milovanović, Tamara, Lukić, Snežana, Milosavljević, Tomica, Srzentić Dražilov, Sanja, Klaassen, Kristel, Pavlović, Sonja, Popović, Dragan, "Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation" in Metabolic Syndrome and Related Disorders, 18, no. 1 (2020):31-38,
https://doi.org/10.1089/met.2019.0090 . .
1
26
9
23

Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy

Stanković, Biljana; Dragasević, Sanja; Klaassen, Kristel; Kotur, Nikola; Srzentić Dražilov, Sanja; Zukić, Branka; Sokic Milutinović, Aleksandra; Milovanović, Tamara; Lukić, Snežana; Popović, Dragan; Pavlović, Sonja; Nikčević, Gordana

(Elsevier Gmbh, Munich, 2020)

TY  - JOUR
AU  - Stanković, Biljana
AU  - Dragasević, Sanja
AU  - Klaassen, Kristel
AU  - Kotur, Nikola
AU  - Srzentić Dražilov, Sanja
AU  - Zukić, Branka
AU  - Sokic Milutinović, Aleksandra
AU  - Milovanović, Tamara
AU  - Lukić, Snežana
AU  - Popović, Dragan
AU  - Pavlović, Sonja
AU  - Nikčević, Gordana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1329
AB  - Background: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. Methods: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Box, Fas and FasL) genes' expression levels by real-time PCR, while NF kappa B transcriptional potency was assessed by electromobility gel shift assay. Results: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Box was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NF kappa B has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. Conclusions: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.
PB  - Elsevier Gmbh, Munich
T2  - Pathology Research and Practice
T1  - Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy
IS  - 6
VL  - 216
DO  - 10.1016/j.prp.2020.152945
ER  - 
@article{
author = "Stanković, Biljana and Dragasević, Sanja and Klaassen, Kristel and Kotur, Nikola and Srzentić Dražilov, Sanja and Zukić, Branka and Sokic Milutinović, Aleksandra and Milovanović, Tamara and Lukić, Snežana and Popović, Dragan and Pavlović, Sonja and Nikčević, Gordana",
year = "2020",
abstract = "Background: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. Methods: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Box, Fas and FasL) genes' expression levels by real-time PCR, while NF kappa B transcriptional potency was assessed by electromobility gel shift assay. Results: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Box was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NF kappa B has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. Conclusions: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.",
publisher = "Elsevier Gmbh, Munich",
journal = "Pathology Research and Practice",
title = "Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy",
number = "6",
volume = "216",
doi = "10.1016/j.prp.2020.152945"
}
Stanković, B., Dragasević, S., Klaassen, K., Kotur, N., Srzentić Dražilov, S., Zukić, B., Sokic Milutinović, A., Milovanović, T., Lukić, S., Popović, D., Pavlović, S.,& Nikčević, G.. (2020). Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy. in Pathology Research and Practice
Elsevier Gmbh, Munich., 216(6).
https://doi.org/10.1016/j.prp.2020.152945
Stanković B, Dragasević S, Klaassen K, Kotur N, Srzentić Dražilov S, Zukić B, Sokic Milutinović A, Milovanović T, Lukić S, Popović D, Pavlović S, Nikčević G. Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy. in Pathology Research and Practice. 2020;216(6).
doi:10.1016/j.prp.2020.152945 .
Stanković, Biljana, Dragasević, Sanja, Klaassen, Kristel, Kotur, Nikola, Srzentić Dražilov, Sanja, Zukić, Branka, Sokic Milutinović, Aleksandra, Milovanović, Tamara, Lukić, Snežana, Popović, Dragan, Pavlović, Sonja, Nikčević, Gordana, "Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy" in Pathology Research and Practice, 216, no. 6 (2020),
https://doi.org/10.1016/j.prp.2020.152945 . .
3
2

Clinical Application of Thiopurine Pharmacogenomics in Pediatrics

Pavlović, Sonja; Kotur, Nikola; Stanković, Biljana; Gašić, Vladimir; Lucafo, Marianna; Decorti, Giuliana; Zukić, Branka

(Bentham Science Publ Ltd, Sharjah, 2020)

TY  - JOUR
AU  - Pavlović, Sonja
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Lucafo, Marianna
AU  - Decorti, Giuliana
AU  - Zukić, Branka
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1408
AB  - Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Drug Metabolism
T1  - Clinical Application of Thiopurine Pharmacogenomics in Pediatrics
EP  - 62
IS  - 1
SP  - 53
VL  - 21
DO  - 10.2174/1389200221666200303113456
ER  - 
@article{
author = "Pavlović, Sonja and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Lucafo, Marianna and Decorti, Giuliana and Zukić, Branka",
year = "2020",
abstract = "Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Drug Metabolism",
title = "Clinical Application of Thiopurine Pharmacogenomics in Pediatrics",
pages = "62-53",
number = "1",
volume = "21",
doi = "10.2174/1389200221666200303113456"
}
Pavlović, S., Kotur, N., Stanković, B., Gašić, V., Lucafo, M., Decorti, G.,& Zukić, B.. (2020). Clinical Application of Thiopurine Pharmacogenomics in Pediatrics. in Current Drug Metabolism
Bentham Science Publ Ltd, Sharjah., 21(1), 53-62.
https://doi.org/10.2174/1389200221666200303113456
Pavlović S, Kotur N, Stanković B, Gašić V, Lucafo M, Decorti G, Zukić B. Clinical Application of Thiopurine Pharmacogenomics in Pediatrics. in Current Drug Metabolism. 2020;21(1):53-62.
doi:10.2174/1389200221666200303113456 .
Pavlović, Sonja, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Lucafo, Marianna, Decorti, Giuliana, Zukić, Branka, "Clinical Application of Thiopurine Pharmacogenomics in Pediatrics" in Current Drug Metabolism, 21, no. 1 (2020):53-62,
https://doi.org/10.2174/1389200221666200303113456 . .
1
6
6

Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients

Buha, Ivana; Skodrić-Trifunović, Vesna; Adžić-Vukicević, Tatjana; Ilić, Aleksandra; Protić, Ana Blanka; Stjepanović, Mihailo; Anđelković, Marina; Vreca, Misa; Milin-Lazović, Jelena; Spasovski, Vesna; Pavlović, Sonja

(J Infection Developing Countries, Tramaniglio, 2019)

TY  - JOUR
AU  - Buha, Ivana
AU  - Skodrić-Trifunović, Vesna
AU  - Adžić-Vukicević, Tatjana
AU  - Ilić, Aleksandra
AU  - Protić, Ana Blanka
AU  - Stjepanović, Mihailo
AU  - Anđelković, Marina
AU  - Vreca, Misa
AU  - Milin-Lazović, Jelena
AU  - Spasovski, Vesna
AU  - Pavlović, Sonja
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1265
AB  - Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. Methodology: We investigated expression of TNF-alpha, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-alpha and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-alpha and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-alpha mRNA were detected in patients with a longer duration of therapy ( gt 2 months) compared to those with a shorter therapy duration ( lt 2 months), and in patients without anemia. Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-alpha gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.
PB  - J Infection Developing Countries, Tramaniglio
T2  - Journal of Infection in Developing Countries
T1  - Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients
EP  - 425
IS  - 5
SP  - 419
VL  - 13
DO  - 10.3855/jidc.10949
ER  - 
@article{
author = "Buha, Ivana and Skodrić-Trifunović, Vesna and Adžić-Vukicević, Tatjana and Ilić, Aleksandra and Protić, Ana Blanka and Stjepanović, Mihailo and Anđelković, Marina and Vreca, Misa and Milin-Lazović, Jelena and Spasovski, Vesna and Pavlović, Sonja",
year = "2019",
abstract = "Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. Methodology: We investigated expression of TNF-alpha, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-alpha and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-alpha and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-alpha mRNA were detected in patients with a longer duration of therapy ( gt 2 months) compared to those with a shorter therapy duration ( lt 2 months), and in patients without anemia. Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-alpha gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.",
publisher = "J Infection Developing Countries, Tramaniglio",
journal = "Journal of Infection in Developing Countries",
title = "Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients",
pages = "425-419",
number = "5",
volume = "13",
doi = "10.3855/jidc.10949"
}
Buha, I., Skodrić-Trifunović, V., Adžić-Vukicević, T., Ilić, A., Protić, A. B., Stjepanović, M., Anđelković, M., Vreca, M., Milin-Lazović, J., Spasovski, V.,& Pavlović, S.. (2019). Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients. in Journal of Infection in Developing Countries
J Infection Developing Countries, Tramaniglio., 13(5), 419-425.
https://doi.org/10.3855/jidc.10949
Buha I, Skodrić-Trifunović V, Adžić-Vukicević T, Ilić A, Protić AB, Stjepanović M, Anđelković M, Vreca M, Milin-Lazović J, Spasovski V, Pavlović S. Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients. in Journal of Infection in Developing Countries. 2019;13(5):419-425.
doi:10.3855/jidc.10949 .
Buha, Ivana, Skodrić-Trifunović, Vesna, Adžić-Vukicević, Tatjana, Ilić, Aleksandra, Protić, Ana Blanka, Stjepanović, Mihailo, Anđelković, Marina, Vreca, Misa, Milin-Lazović, Jelena, Spasovski, Vesna, Pavlović, Sonja, "Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients" in Journal of Infection in Developing Countries, 13, no. 5 (2019):419-425,
https://doi.org/10.3855/jidc.10949 . .
1
10
10

Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers

Stjepanović, Mihailo I.; Mihailović-Vucinić, Violeta; Spasovski, Vesna; Milin-Lazović, Jelena; Skodrić-Trifunović, Vesna; Stanković, Sanja; Anđelković, Marina; Komazec, Jovana; Momcilović, Ana; Santrić-Milicević, Milena; Pavlović, Sonja

(Termedia Publishing House Ltd, Poznan, 2019)

TY  - JOUR
AU  - Stjepanović, Mihailo I.
AU  - Mihailović-Vucinić, Violeta
AU  - Spasovski, Vesna
AU  - Milin-Lazović, Jelena
AU  - Skodrić-Trifunović, Vesna
AU  - Stanković, Sanja
AU  - Anđelković, Marina
AU  - Komazec, Jovana
AU  - Momcilović, Ana
AU  - Santrić-Milicević, Milena
AU  - Pavlović, Sonja
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1210
AB  - Introduction: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients. Material and methods: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method. Results: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients. Conclusions: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis.
PB  - Termedia Publishing House Ltd, Poznan
T2  - Archives of Medical Science
T1  - Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers
EP  - 1146
IS  - 5
SP  - 1138
VL  - 15
DO  - 10.5114/aoms.2018.79682
ER  - 
@article{
author = "Stjepanović, Mihailo I. and Mihailović-Vucinić, Violeta and Spasovski, Vesna and Milin-Lazović, Jelena and Skodrić-Trifunović, Vesna and Stanković, Sanja and Anđelković, Marina and Komazec, Jovana and Momcilović, Ana and Santrić-Milicević, Milena and Pavlović, Sonja",
year = "2019",
abstract = "Introduction: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients. Material and methods: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method. Results: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients. Conclusions: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis.",
publisher = "Termedia Publishing House Ltd, Poznan",
journal = "Archives of Medical Science",
title = "Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers",
pages = "1146-1138",
number = "5",
volume = "15",
doi = "10.5114/aoms.2018.79682"
}
Stjepanović, M. I., Mihailović-Vucinić, V., Spasovski, V., Milin-Lazović, J., Skodrić-Trifunović, V., Stanković, S., Anđelković, M., Komazec, J., Momcilović, A., Santrić-Milicević, M.,& Pavlović, S.. (2019). Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers. in Archives of Medical Science
Termedia Publishing House Ltd, Poznan., 15(5), 1138-1146.
https://doi.org/10.5114/aoms.2018.79682
Stjepanović MI, Mihailović-Vucinić V, Spasovski V, Milin-Lazović J, Skodrić-Trifunović V, Stanković S, Anđelković M, Komazec J, Momcilović A, Santrić-Milicević M, Pavlović S. Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers. in Archives of Medical Science. 2019;15(5):1138-1146.
doi:10.5114/aoms.2018.79682 .
Stjepanović, Mihailo I., Mihailović-Vucinić, Violeta, Spasovski, Vesna, Milin-Lazović, Jelena, Skodrić-Trifunović, Vesna, Stanković, Sanja, Anđelković, Marina, Komazec, Jovana, Momcilović, Ana, Santrić-Milicević, Milena, Pavlović, Sonja, "Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers" in Archives of Medical Science, 15, no. 5 (2019):1138-1146,
https://doi.org/10.5114/aoms.2018.79682 . .
1
9
9

Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation

Loncarić, Darija; Stanković, Biljana; Ghousein, Amani; Vreca, Misa; Spasovski, Vesna; Villacreces, Arnaud; Debeissat, Christelle; Grosset, Christophe F.; Ivanović, Zoran; Pavlović, Sonja

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

TY  - JOUR
AU  - Loncarić, Darija
AU  - Stanković, Biljana
AU  - Ghousein, Amani
AU  - Vreca, Misa
AU  - Spasovski, Vesna
AU  - Villacreces, Arnaud
AU  - Debeissat, Christelle
AU  - Grosset, Christophe F.
AU  - Ivanović, Zoran
AU  - Pavlović, Sonja
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1263
AB  - A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning (LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1 alpha and HIF-2 alpha gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p lt 0.05). Knocking down of HIF-1 alpha and HIF-2 alpha genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation
EP  - 208
IS  - 2
SP  - 201
VL  - 71
DO  - 10.2298/ABS181117001L
ER  - 
@article{
author = "Loncarić, Darija and Stanković, Biljana and Ghousein, Amani and Vreca, Misa and Spasovski, Vesna and Villacreces, Arnaud and Debeissat, Christelle and Grosset, Christophe F. and Ivanović, Zoran and Pavlović, Sonja",
year = "2019",
abstract = "A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning (LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1 alpha and HIF-2 alpha gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p lt 0.05). Knocking down of HIF-1 alpha and HIF-2 alpha genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation",
pages = "208-201",
number = "2",
volume = "71",
doi = "10.2298/ABS181117001L"
}
Loncarić, D., Stanković, B., Ghousein, A., Vreca, M., Spasovski, V., Villacreces, A., Debeissat, C., Grosset, C. F., Ivanović, Z.,& Pavlović, S.. (2019). Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 71(2), 201-208.
https://doi.org/10.2298/ABS181117001L
Loncarić D, Stanković B, Ghousein A, Vreca M, Spasovski V, Villacreces A, Debeissat C, Grosset CF, Ivanović Z, Pavlović S. Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation. in Archives of Biological Sciences. 2019;71(2):201-208.
doi:10.2298/ABS181117001L .
Loncarić, Darija, Stanković, Biljana, Ghousein, Amani, Vreca, Misa, Spasovski, Vesna, Villacreces, Arnaud, Debeissat, Christelle, Grosset, Christophe F., Ivanović, Zoran, Pavlović, Sonja, "Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation" in Archives of Biological Sciences, 71, no. 2 (2019):201-208,
https://doi.org/10.2298/ABS181117001L . .
1
1

Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije

Gašić, Vladimir; Stanković, Biljana; Zukić, Branka; Janić, Dragana; Dokmanović, Lidija; Krstovski, Nada; Lazić, Jelena; Milošević, Goran; Lucafò, Marianna; Stocco, Gabriele; Decorti, Giuliana; Pavlović, Sonja; Kotur, Nikola

(Društvo medicinskih biohemičara Srbije, Beograd i Versita, 2019)

TY  - JOUR
AU  - Gašić, Vladimir
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Janić, Dragana
AU  - Dokmanović, Lidija
AU  - Krstovski, Nada
AU  - Lazić, Jelena
AU  - Milošević, Goran
AU  - Lucafò, Marianna
AU  - Stocco, Gabriele
AU  - Decorti, Giuliana
AU  - Pavlović, Sonja
AU  - Kotur, Nikola
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1269
AB  - Uvod: Ekspresija duge nekodirajuće RNK G AS5 je izme - njena u mnogim kancerima zbog njene uloge u apoptozi i inhibiciji rasta ćelije. G AS5 interaguje sa glukokortikoidnim receptorom, što je čini potencijalnim farmakotranskripcionim markerom značajnim za glukokortikoidnu terapiju. Naš cilj u ovoj studiji je bio da analiziramo ekspresiju GAS5 tokom indukcione terapije kod dečje akutne limfoblastne leukemije (ALL), u kojoj se koriste glukokortikoidni lekovi, i da te rezultate povežemo sa odgovorom na terapiju. Metode: Nivo ekspresije G AS5 u mononuklearnim ćelijama periferne krvi izolovanih od 29 dece obolelih od ALL, određen je metodologijom RT-qPCR, i to u momentu dijagnoze, 15. i 33. dana indukcione terapije. Rezultati: Naši rezultati su pokazali da postoje interindivi - dualne razlike u ekspresiji GAS5 kod pacijenata, i to u svim analiziranim tačkama. Kod svakog ALL pacijenta GAS5 ekspresija je 15. dana bila visa u odnosu na ekspresiju u momentu dijagnoze (p  lt  0,0005). Nivo ekspresije GAS5 je 33. dana bio niži u poređenju sa 15. danom (p  lt  0,0005), ali je i dalje bio značajno visi u odnosu na momenat dijagnoze kod većine pacijenata (p = 0,001). Pacijenti čiji je broj blasta u perifernoj krvi 8. dana bio ispod 100 po mikrolitru periferne krvi, imali su viši nivo ekspresije GAS5 (p = 0,016) i niži odnos ekspresija merenih 15. dana i u momentu dijagnoze (p = 0,009). Zaključak: Nasi rezultati ukazuju da bi nivo ekspresije GAS5 mogao da bude marker terapijskog odgovora u indukcionoj terapiji kod dece obolele od ALL.
AB  - Background: Long non-coding RNA growth arrest-specific 5 (GAS5) is deregulated in many cancers because of its role in cell growth arrest and apoptosis. Additionally, GAS5 interacts with glucocorticoid receptor, making it a potential pharmacotranscription marker of glucocorticoid (GC) therapy. In this study, we aimed at analysing G AS5 expression in the remission induction therapy phase of childhood acute lymphoblastic leukemia (ALL), in which GCs are mandatorily used, and to correlate it with therapy response. Methods: G AS5 expression was measured in peripheral blood mononuclear cells taken from 29 childhood ALL patients at diagnosis, on day 15 and day 33 of remission induction therapy using RT-qPCR methodology. Results: Our results have shown interindividual differences in G AS5 expression at all time points. For each ALL patient, G A S5 expression was higher on day 15 in comparison to its level at diagnosis (p lt 0.0005). On day 33, the level of G A S5 expression decreased in comparison with day 15 (p lt 0.0005), but it was still significantly higher than at diagnosis for the majority of patients (p=0.001). Patients whose number of blasts on day 8 was below 100 per mL of peripheral blood had a higher GAS5 expression at diagnosis (p=0.016), and lower ratio day 15/diagnosis (p=0.009). Conclusions: Our results suggest that the expression level of GAS5 could be a potential marker of therapy response in remission induction therapy of childhood ALL.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije
T1  - Expression pattern of long non-coding RNA growth arrest-specific 5 in the remission induction therapy in childhood acute lymphoblastic leukemia
EP  - 298
IS  - 3
SP  - 292
VL  - 38
DO  - 10.2478/jomb-2018-0038
ER  - 
@article{
author = "Gašić, Vladimir and Stanković, Biljana and Zukić, Branka and Janić, Dragana and Dokmanović, Lidija and Krstovski, Nada and Lazić, Jelena and Milošević, Goran and Lucafò, Marianna and Stocco, Gabriele and Decorti, Giuliana and Pavlović, Sonja and Kotur, Nikola",
year = "2019",
abstract = "Uvod: Ekspresija duge nekodirajuće RNK G AS5 je izme - njena u mnogim kancerima zbog njene uloge u apoptozi i inhibiciji rasta ćelije. G AS5 interaguje sa glukokortikoidnim receptorom, što je čini potencijalnim farmakotranskripcionim markerom značajnim za glukokortikoidnu terapiju. Naš cilj u ovoj studiji je bio da analiziramo ekspresiju GAS5 tokom indukcione terapije kod dečje akutne limfoblastne leukemije (ALL), u kojoj se koriste glukokortikoidni lekovi, i da te rezultate povežemo sa odgovorom na terapiju. Metode: Nivo ekspresije G AS5 u mononuklearnim ćelijama periferne krvi izolovanih od 29 dece obolelih od ALL, određen je metodologijom RT-qPCR, i to u momentu dijagnoze, 15. i 33. dana indukcione terapije. Rezultati: Naši rezultati su pokazali da postoje interindivi - dualne razlike u ekspresiji GAS5 kod pacijenata, i to u svim analiziranim tačkama. Kod svakog ALL pacijenta GAS5 ekspresija je 15. dana bila visa u odnosu na ekspresiju u momentu dijagnoze (p  lt  0,0005). Nivo ekspresije GAS5 je 33. dana bio niži u poređenju sa 15. danom (p  lt  0,0005), ali je i dalje bio značajno visi u odnosu na momenat dijagnoze kod većine pacijenata (p = 0,001). Pacijenti čiji je broj blasta u perifernoj krvi 8. dana bio ispod 100 po mikrolitru periferne krvi, imali su viši nivo ekspresije GAS5 (p = 0,016) i niži odnos ekspresija merenih 15. dana i u momentu dijagnoze (p = 0,009). Zaključak: Nasi rezultati ukazuju da bi nivo ekspresije GAS5 mogao da bude marker terapijskog odgovora u indukcionoj terapiji kod dece obolele od ALL., Background: Long non-coding RNA growth arrest-specific 5 (GAS5) is deregulated in many cancers because of its role in cell growth arrest and apoptosis. Additionally, GAS5 interacts with glucocorticoid receptor, making it a potential pharmacotranscription marker of glucocorticoid (GC) therapy. In this study, we aimed at analysing G AS5 expression in the remission induction therapy phase of childhood acute lymphoblastic leukemia (ALL), in which GCs are mandatorily used, and to correlate it with therapy response. Methods: G AS5 expression was measured in peripheral blood mononuclear cells taken from 29 childhood ALL patients at diagnosis, on day 15 and day 33 of remission induction therapy using RT-qPCR methodology. Results: Our results have shown interindividual differences in G AS5 expression at all time points. For each ALL patient, G A S5 expression was higher on day 15 in comparison to its level at diagnosis (p lt 0.0005). On day 33, the level of G A S5 expression decreased in comparison with day 15 (p lt 0.0005), but it was still significantly higher than at diagnosis for the majority of patients (p=0.001). Patients whose number of blasts on day 8 was below 100 per mL of peripheral blood had a higher GAS5 expression at diagnosis (p=0.016), and lower ratio day 15/diagnosis (p=0.009). Conclusions: Our results suggest that the expression level of GAS5 could be a potential marker of therapy response in remission induction therapy of childhood ALL.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije, Expression pattern of long non-coding RNA growth arrest-specific 5 in the remission induction therapy in childhood acute lymphoblastic leukemia",
pages = "298-292",
number = "3",
volume = "38",
doi = "10.2478/jomb-2018-0038"
}
Gašić, V., Stanković, B., Zukić, B., Janić, D., Dokmanović, L., Krstovski, N., Lazić, J., Milošević, G., Lucafò, M., Stocco, G., Decorti, G., Pavlović, S.,& Kotur, N.. (2019). Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 38(3), 292-298.
https://doi.org/10.2478/jomb-2018-0038
Gašić V, Stanković B, Zukić B, Janić D, Dokmanović L, Krstovski N, Lazić J, Milošević G, Lucafò M, Stocco G, Decorti G, Pavlović S, Kotur N. Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije. in Journal of Medical Biochemistry. 2019;38(3):292-298.
doi:10.2478/jomb-2018-0038 .
Gašić, Vladimir, Stanković, Biljana, Zukić, Branka, Janić, Dragana, Dokmanović, Lidija, Krstovski, Nada, Lazić, Jelena, Milošević, Goran, Lucafò, Marianna, Stocco, Gabriele, Decorti, Giuliana, Pavlović, Sonja, Kotur, Nikola, "Ekspresioni obrazac duge nekodirajuće RNK growth arrest specific 5 u fazi indukcije u terapiji dečje akutne limfoblastne leukemije" in Journal of Medical Biochemistry, 38, no. 3 (2019):292-298,
https://doi.org/10.2478/jomb-2018-0038 . .
25
3
21

Genomski profil pacijenata dečijeg uzrasta sa hepatičnim glikogenozama: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih varijanti

Skakić, Anita

(Univerzitet u Beogradu, Biološki fakultet, 2019)

TY  - THES
AU  - Skakić, Anita
PY  - 2019
UR  - https://nardus.mpn.gov.rs/handle/123456789/11505
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=6912
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:20261/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025219250
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/56
AB  - Bolesti koje nastaju usled naslednog enzimskog poremećaja u sintezi ili razgradnji glikogena i koje primarno pogađaju jetru i bubrege, nazivaju se hepatične glikogenoze. Glikogenoza tip I (GSD tip I) je jedan od najčešćih oblika i zauzima posebno mesto u grupi ovih bolesti zbog prepoznatljivog kliničkog fenotipa koji jasno odražava složenu patofoziologiju poremećaja u metabolizmu glikogena. GSD tip Ia razvija se usled deficitarne aktivnosti enzima glukozo-6-fosfataze α (G6Paza-α ili G6PC), a GSD tip Ib nastaje kao posledica deficijencije transportera glukozo-6-fosfat translokaze (G6PT ili SLC37A4) koja se nalazi na membrani endoplazmatičnog retikuluma (ER). U jetri, bubrezima i mukozi creva, G6Paza-α i G6PT formiraju funkcionalni kompleks koji učestvuje u održavanju homeostaze glukoze u krvi između obroka. Ukoliko je ovaj proces narušen, dolazi do nakupljanja glikogena u jetri, bubrezima i intestinalnoj mukozi i razvoja hipoglikemije, hiperlaktatemije, hiperlipidemije, hiperurikemije, i hepatonefromegalije. Ove metaboličke abnormalnosti rezultiraju dugoročnim komplikacijama bubrežnih bolesti i hepatocelularnih adenoma/karcinoma, čiji su molekularni mehanizmi slabo istraženi. Kod pacijenata obolelih od GSD tip Ib dodatno se javlјaju neutropenija i disfunkcija neutrofila i makrofaga, pa zbog toga ovi pacijenti razvijaju rekurentne bakterijske infekcije, neretko praćene simptomima inflamatorne bolesti creva slične Kronovoj bolesti. Uzimajući u obzir patofiziološke posledice metaboličkog stresa kod pacijenata obolelih od GSD tip Ib, od velikog interesa su adaptivni odgovori i molekularni mehanizmi koje ćelije aktiviraju pod takvim uslovima. Poznato je da poremećaj homeostaze ER-a, nastalog kao posledica gubitka intraćelijske produkcije glukoze, dovodi do hronične aktivacije „odgovora nesavijenih proteina” (UPR) čime doprinosi patogenezi mnogih bolesti. Stres ER-a je impliciran u mnogim hroničnim bolestima, ali se vrlo malo zna o hroničnom stresu ER-a uzrokovanog nedostatkom G6PT. Osim GSD tip I, postoji još šest hepatičnih GSD (tipovi 0, III, IV, VI, IX i XI), kao i desetine tipova GSD koje pogađaju skeletne mišiće, srce i druge organe. Pošto su posledice bolesti ozbilјne i ireverzibilne, molekularno-genetičko testiranje je od presudne važnosti za precizno postavlјanje dijagnoze i što raniju primenu adekvatne terapije...
AB  - Hepatic glycogen storage diseases (GSD) are inherited disorders of glycogen synthesis or degradation, which primarily affect the liver and kidneys. GSD type I is one of the most common types and takes a special place in the group of these diseases due to a recognizable clinical phenotype that clearly reflects the complex pathophysiology of disorders in glycogen metabolism. GSD type Ia and type Ib are due to a deficiency of an enzyme glucose-6-phosphatase α (G6Pase-α or G6PC) and endoplasmic reticulum (ER) glucose-6-phosphate translocase (G6PT or SLC37A4), respectively. G6Pase-α and G6PT form a functional complex on the ER membrane, that maintenance the blood glucose homeostasis between the meals, and its deficiency results in excessive accumulation of glycogen in the liver, kidney, and intestinal mucosa, leading to the hypoglycemia, hyperlactatemia, hyperlipidemia, hyperuricemia, and hepathonephromegaly. These metabolic abnormalities result in long-term complications of kidney diseases and hepatocellular adenomas/carcinoma, whose molecular mechanisms are poorly understood. Patients with GSD type Ib, also develop neutropenia and dysfunction of neutrophils and macrophages followed by recurrent bacterial infections, and symptoms of inflammatory bowel disease like Crohn’s disease. Considering the pathophysiological consequences of this metabolic stress, the adaptive responses and molecular markers which cells activate under such conditions are of great interest. It is known that disturbance of ER homeostasis, resulting from a loss of intracellular glucose production, leads to the chronic activation of the unfolded protein response (UPR), which contributes to the pathogenesis of many diseases. ER stress is implicated in many chronic diseases, but little is known how the UPR corresponds to the chronic ER stress caused by a deficiency of G6PT. Besides GSD type I, there are six additional hepatic GSD types (0, III, IV, VI, IX and XI), as well as dozens of GSD forms that affect skeletal muscles, heart and other organs. Since the consequences of the disease are serious and irreversible, molecular-genetic testing is crucial for precise diagnosis and applying the appropriate therapy as early as possible...
PB  - Univerzitet u Beogradu, Biološki fakultet
T1  - Genomski profil pacijenata dečijeg uzrasta sa hepatičnim glikogenozama: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih varijanti
T1  - Genomic profiling of pediatric patients with liver glycogenosis: genotype-phenotype correlation and functional characterization of novel variants
UR  - https://hdl.handle.net/21.15107/rcub_nardus_11505
ER  - 
@phdthesis{
author = "Skakić, Anita",
year = "2019",
abstract = "Bolesti koje nastaju usled naslednog enzimskog poremećaja u sintezi ili razgradnji glikogena i koje primarno pogađaju jetru i bubrege, nazivaju se hepatične glikogenoze. Glikogenoza tip I (GSD tip I) je jedan od najčešćih oblika i zauzima posebno mesto u grupi ovih bolesti zbog prepoznatljivog kliničkog fenotipa koji jasno odražava složenu patofoziologiju poremećaja u metabolizmu glikogena. GSD tip Ia razvija se usled deficitarne aktivnosti enzima glukozo-6-fosfataze α (G6Paza-α ili G6PC), a GSD tip Ib nastaje kao posledica deficijencije transportera glukozo-6-fosfat translokaze (G6PT ili SLC37A4) koja se nalazi na membrani endoplazmatičnog retikuluma (ER). U jetri, bubrezima i mukozi creva, G6Paza-α i G6PT formiraju funkcionalni kompleks koji učestvuje u održavanju homeostaze glukoze u krvi između obroka. Ukoliko je ovaj proces narušen, dolazi do nakupljanja glikogena u jetri, bubrezima i intestinalnoj mukozi i razvoja hipoglikemije, hiperlaktatemije, hiperlipidemije, hiperurikemije, i hepatonefromegalije. Ove metaboličke abnormalnosti rezultiraju dugoročnim komplikacijama bubrežnih bolesti i hepatocelularnih adenoma/karcinoma, čiji su molekularni mehanizmi slabo istraženi. Kod pacijenata obolelih od GSD tip Ib dodatno se javlјaju neutropenija i disfunkcija neutrofila i makrofaga, pa zbog toga ovi pacijenti razvijaju rekurentne bakterijske infekcije, neretko praćene simptomima inflamatorne bolesti creva slične Kronovoj bolesti. Uzimajući u obzir patofiziološke posledice metaboličkog stresa kod pacijenata obolelih od GSD tip Ib, od velikog interesa su adaptivni odgovori i molekularni mehanizmi koje ćelije aktiviraju pod takvim uslovima. Poznato je da poremećaj homeostaze ER-a, nastalog kao posledica gubitka intraćelijske produkcije glukoze, dovodi do hronične aktivacije „odgovora nesavijenih proteina” (UPR) čime doprinosi patogenezi mnogih bolesti. Stres ER-a je impliciran u mnogim hroničnim bolestima, ali se vrlo malo zna o hroničnom stresu ER-a uzrokovanog nedostatkom G6PT. Osim GSD tip I, postoji još šest hepatičnih GSD (tipovi 0, III, IV, VI, IX i XI), kao i desetine tipova GSD koje pogađaju skeletne mišiće, srce i druge organe. Pošto su posledice bolesti ozbilјne i ireverzibilne, molekularno-genetičko testiranje je od presudne važnosti za precizno postavlјanje dijagnoze i što raniju primenu adekvatne terapije..., Hepatic glycogen storage diseases (GSD) are inherited disorders of glycogen synthesis or degradation, which primarily affect the liver and kidneys. GSD type I is one of the most common types and takes a special place in the group of these diseases due to a recognizable clinical phenotype that clearly reflects the complex pathophysiology of disorders in glycogen metabolism. GSD type Ia and type Ib are due to a deficiency of an enzyme glucose-6-phosphatase α (G6Pase-α or G6PC) and endoplasmic reticulum (ER) glucose-6-phosphate translocase (G6PT or SLC37A4), respectively. G6Pase-α and G6PT form a functional complex on the ER membrane, that maintenance the blood glucose homeostasis between the meals, and its deficiency results in excessive accumulation of glycogen in the liver, kidney, and intestinal mucosa, leading to the hypoglycemia, hyperlactatemia, hyperlipidemia, hyperuricemia, and hepathonephromegaly. These metabolic abnormalities result in long-term complications of kidney diseases and hepatocellular adenomas/carcinoma, whose molecular mechanisms are poorly understood. Patients with GSD type Ib, also develop neutropenia and dysfunction of neutrophils and macrophages followed by recurrent bacterial infections, and symptoms of inflammatory bowel disease like Crohn’s disease. Considering the pathophysiological consequences of this metabolic stress, the adaptive responses and molecular markers which cells activate under such conditions are of great interest. It is known that disturbance of ER homeostasis, resulting from a loss of intracellular glucose production, leads to the chronic activation of the unfolded protein response (UPR), which contributes to the pathogenesis of many diseases. ER stress is implicated in many chronic diseases, but little is known how the UPR corresponds to the chronic ER stress caused by a deficiency of G6PT. Besides GSD type I, there are six additional hepatic GSD types (0, III, IV, VI, IX and XI), as well as dozens of GSD forms that affect skeletal muscles, heart and other organs. Since the consequences of the disease are serious and irreversible, molecular-genetic testing is crucial for precise diagnosis and applying the appropriate therapy as early as possible...",
publisher = "Univerzitet u Beogradu, Biološki fakultet",
title = "Genomski profil pacijenata dečijeg uzrasta sa hepatičnim glikogenozama: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih varijanti, Genomic profiling of pediatric patients with liver glycogenosis: genotype-phenotype correlation and functional characterization of novel variants",
url = "https://hdl.handle.net/21.15107/rcub_nardus_11505"
}
Skakić, A.. (2019). Genomski profil pacijenata dečijeg uzrasta sa hepatičnim glikogenozama: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih varijanti. 
Univerzitet u Beogradu, Biološki fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_11505
Skakić A. Genomski profil pacijenata dečijeg uzrasta sa hepatičnim glikogenozama: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih varijanti. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_11505 .
Skakić, Anita, "Genomski profil pacijenata dečijeg uzrasta sa hepatičnim glikogenozama: korelacija genotipa i fenotipa i funkcionalna karakterizacija novih varijanti" (2019),
https://hdl.handle.net/21.15107/rcub_nardus_11505 .