Jekić, Biljana

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  • Jekić, Biljana (11)
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Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients

Vejnović, Dubravka; Milić, Vera; Popović, Branka; Damnjanović, Tatjana; Maksimović, Nela; Bunjevački, Vera; Krajinović, Maja; Novaković, Ivana; Damjanov, Nemanja; Jekić, Biljana

(Taylor & Francis Ltd, Abingdon, 2019)

TY  - JOUR
AU  - Vejnović, Dubravka
AU  - Milić, Vera
AU  - Popović, Branka
AU  - Damnjanović, Tatjana
AU  - Maksimović, Nela
AU  - Bunjevački, Vera
AU  - Krajinović, Maja
AU  - Novaković, Ivana
AU  - Damjanov, Nemanja
AU  - Jekić, Biljana
PY  - 2019
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2526
AB  - Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).
PB  - Taylor & Francis Ltd, Abingdon
T2  - Expert Opinion on Drug Metabolism & Toxicology
T1  - Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients
VL  - 15
IS  - 3
SP  - 253
EP  - 257
DO  - 10.1080/17425255.2019.1563594
ER  - 
@article{
author = "Vejnović, Dubravka and Milić, Vera and Popović, Branka and Damnjanović, Tatjana and Maksimović, Nela and Bunjevački, Vera and Krajinović, Maja and Novaković, Ivana and Damjanov, Nemanja and Jekić, Biljana",
year = "2019",
abstract = "Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Expert Opinion on Drug Metabolism & Toxicology",
title = "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients",
volume = "15",
number = "3",
pages = "253-257",
doi = "10.1080/17425255.2019.1563594"
}
Vejnović, D., Milić, V., Popović, B., Damnjanović, T., Maksimović, N., Bunjevački, V., Krajinović, M., Novaković, I., Damjanov, N.,& Jekić, B.. (2019). Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology
Taylor & Francis Ltd, Abingdon., 15(3), 253-257.
https://doi.org/10.1080/17425255.2019.1563594
Vejnović D, Milić V, Popović B, Damnjanović T, Maksimović N, Bunjevački V, Krajinović M, Novaković I, Damjanov N, Jekić B. Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology. 2019;15(3):253-257.
doi:10.1080/17425255.2019.1563594 .
Vejnović, Dubravka, Milić, Vera, Popović, Branka, Damnjanović, Tatjana, Maksimović, Nela, Bunjevački, Vera, Krajinović, Maja, Novaković, Ivana, Damjanov, Nemanja, Jekić, Biljana, "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients" in Expert Opinion on Drug Metabolism & Toxicology, 15, no. 3 (2019):253-257,
https://doi.org/10.1080/17425255.2019.1563594 . .
4
3
4

Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients

Vejnović, Dubravka; Milić, Vera; Popović, Branka; Damnjanović, Tatjana; Maksimović, Nela; Bunjevački, Vera; Krajinović, Maja; Novaković, Ivana; Damjanov, Nemanja; Jekić, Biljana

(Taylor & Francis Ltd, Abingdon, 2019)

TY  - JOUR
AU  - Vejnović, Dubravka
AU  - Milić, Vera
AU  - Popović, Branka
AU  - Damnjanović, Tatjana
AU  - Maksimović, Nela
AU  - Bunjevački, Vera
AU  - Krajinović, Maja
AU  - Novaković, Ivana
AU  - Damjanov, Nemanja
AU  - Jekić, Biljana
PY  - 2019
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2462
AB  - Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).
PB  - Taylor & Francis Ltd, Abingdon
T2  - Expert Opinion on Drug Metabolism & Toxicology
T1  - Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients
VL  - 15
IS  - 3
SP  - 253
EP  - 257
DO  - 10.1080/17425255.2019.1563594
ER  - 
@article{
author = "Vejnović, Dubravka and Milić, Vera and Popović, Branka and Damnjanović, Tatjana and Maksimović, Nela and Bunjevački, Vera and Krajinović, Maja and Novaković, Ivana and Damjanov, Nemanja and Jekić, Biljana",
year = "2019",
abstract = "Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Expert Opinion on Drug Metabolism & Toxicology",
title = "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients",
volume = "15",
number = "3",
pages = "253-257",
doi = "10.1080/17425255.2019.1563594"
}
Vejnović, D., Milić, V., Popović, B., Damnjanović, T., Maksimović, N., Bunjevački, V., Krajinović, M., Novaković, I., Damjanov, N.,& Jekić, B.. (2019). Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology
Taylor & Francis Ltd, Abingdon., 15(3), 253-257.
https://doi.org/10.1080/17425255.2019.1563594
Vejnović D, Milić V, Popović B, Damnjanović T, Maksimović N, Bunjevački V, Krajinović M, Novaković I, Damjanov N, Jekić B. Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology. 2019;15(3):253-257.
doi:10.1080/17425255.2019.1563594 .
Vejnović, Dubravka, Milić, Vera, Popović, Branka, Damnjanović, Tatjana, Maksimović, Nela, Bunjevački, Vera, Krajinović, Maja, Novaković, Ivana, Damjanov, Nemanja, Jekić, Biljana, "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients" in Expert Opinion on Drug Metabolism & Toxicology, 15, no. 3 (2019):253-257,
https://doi.org/10.1080/17425255.2019.1563594 . .
4
3
4

Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients

Jekić, Biljana; Luković, Ljiljana; Bunjevački, Vera; Milić, Vera; Novaković, Ivana; Damnjanović, Tatjana; Milašin, Jelena; Popović, Branka; Maksimović, Nela; Damjanov, Nemanja; Radunović, Goran; Kovacević, Ljiljana; Krajinović, Maja

(Springer Heidelberg, Heidelberg, 2013)

TY  - JOUR
AU  - Jekić, Biljana
AU  - Luković, Ljiljana
AU  - Bunjevački, Vera
AU  - Milić, Vera
AU  - Novaković, Ivana
AU  - Damnjanović, Tatjana
AU  - Milašin, Jelena
AU  - Popović, Branka
AU  - Maksimović, Nela
AU  - Damjanov, Nemanja
AU  - Radunović, Goran
AU  - Kovacević, Ljiljana
AU  - Krajinović, Maja
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1839
AB  - Purpose Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). Methods The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G>T and 452 C>T), CCND1 (870 A>G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as nonresponders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p=0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p=0.003). No other significant association were observed. Conclusion The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T>G polymorphism may have high predictive value for myelosuppression in RA patients.
PB  - Springer Heidelberg, Heidelberg
T2  - European Journal of Clinical Pharmacology
T1  - Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients
VL  - 69
IS  - 3
SP  - 377
EP  - 383
DO  - 10.1007/s00228-012-1341-3
ER  - 
@article{
author = "Jekić, Biljana and Luković, Ljiljana and Bunjevački, Vera and Milić, Vera and Novaković, Ivana and Damnjanović, Tatjana and Milašin, Jelena and Popović, Branka and Maksimović, Nela and Damjanov, Nemanja and Radunović, Goran and Kovacević, Ljiljana and Krajinović, Maja",
year = "2013",
abstract = "Purpose Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). Methods The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G>T and 452 C>T), CCND1 (870 A>G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as nonresponders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p=0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p=0.003). No other significant association were observed. Conclusion The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T>G polymorphism may have high predictive value for myelosuppression in RA patients.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "European Journal of Clinical Pharmacology",
title = "Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients",
volume = "69",
number = "3",
pages = "377-383",
doi = "10.1007/s00228-012-1341-3"
}
Jekić, B., Luković, L., Bunjevački, V., Milić, V., Novaković, I., Damnjanović, T., Milašin, J., Popović, B., Maksimović, N., Damjanov, N., Radunović, G., Kovacević, L.,& Krajinović, M.. (2013). Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. in European Journal of Clinical Pharmacology
Springer Heidelberg, Heidelberg., 69(3), 377-383.
https://doi.org/10.1007/s00228-012-1341-3
Jekić B, Luković L, Bunjevački V, Milić V, Novaković I, Damnjanović T, Milašin J, Popović B, Maksimović N, Damjanov N, Radunović G, Kovacević L, Krajinović M. Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. in European Journal of Clinical Pharmacology. 2013;69(3):377-383.
doi:10.1007/s00228-012-1341-3 .
Jekić, Biljana, Luković, Ljiljana, Bunjevački, Vera, Milić, Vera, Novaković, Ivana, Damnjanović, Tatjana, Milašin, Jelena, Popović, Branka, Maksimović, Nela, Damjanov, Nemanja, Radunović, Goran, Kovacević, Ljiljana, Krajinović, Maja, "Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients" in European Journal of Clinical Pharmacology, 69, no. 3 (2013):377-383,
https://doi.org/10.1007/s00228-012-1341-3 . .
47
41
47

Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis

Milić, Vera; Jekić, Biljana; Luković, Ljiljana; Bunjevački, Vera; Milašin, Jelena; Novaković, I.; Damnjanović, Tatjana; Popović, Branka; Maksimović, Nela; Damjanov, Nemanja; Radunović, Goran; Pejnović, Nada; Krajinović, Maja

(Clinical & Exper Rheumatology, Pisa, 2012)

TY  - JOUR
AU  - Milić, Vera
AU  - Jekić, Biljana
AU  - Luković, Ljiljana
AU  - Bunjevački, Vera
AU  - Milašin, Jelena
AU  - Novaković, I.
AU  - Damnjanović, Tatjana
AU  - Popović, Branka
AU  - Maksimović, Nela
AU  - Damjanov, Nemanja
AU  - Radunović, Goran
AU  - Pejnović, Nada
AU  - Krajinović, Maja
PY  - 2012
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1741
AB  - Objectives Identifying genetic predictors of methotrexate (MTX) treatment response in patients with rheumatoid arthritis (RA) may have great importance for optimising drug doses required for clinical benefit without toxicity. In a group of 125 RA patients treated with MTX we investigated whether selected polymorphisms in genes relevant for MTX action (aminoimidazole-4-carboxiamide ribonucleotide transformylase, ATIC, and dihydrofolate reductase, DHFR) modulate disease activity and/or have impact on therapy side effects. Methods The efficacy of treatment was estimated both by the disease activity score in 28 joints (DAS28), based on EULAR criteria, and relative DAS28 (rDAS28) score. Adverse drug events (ADEs) were also recorded. RA patients were genotyped using the PCR-RFLP method, followed by an association study between ATIC -129T>G, DHFR -216T>C and DHFR -317A>G polymorphisms and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 96 RA patients (76.8%) were classified as responders (good/moderate response) and 29 (23.2%) as non-responders (poor response). rDAS28 values ranged from -0.01 to 0.80 (mean value 0.31 +/- 0.19). Among 125 patients enrolled in this study 39 experienced at least one side effect. The DHFR -317AA genotype was associated with the less favourable response (reduction in rDAS28 score, p=0.05). None of the analysed polymorphisms was associated with MTX toxicity. Conclusion RA patients with DHFR-317AA genotype had less favourable response to MTX Further studies in larger patient populations are necessary to confirm the relationship between the analysed polymorphisms and MTX treatment response.
PB  - Clinical & Exper Rheumatology, Pisa
T2  - Clinical & Experimental Rheumatology
T1  - Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis
VL  - 30
IS  - 2
SP  - 178
EP  - 183
UR  - https://hdl.handle.net/21.15107/rcub_smile_1741
ER  - 
@article{
author = "Milić, Vera and Jekić, Biljana and Luković, Ljiljana and Bunjevački, Vera and Milašin, Jelena and Novaković, I. and Damnjanović, Tatjana and Popović, Branka and Maksimović, Nela and Damjanov, Nemanja and Radunović, Goran and Pejnović, Nada and Krajinović, Maja",
year = "2012",
abstract = "Objectives Identifying genetic predictors of methotrexate (MTX) treatment response in patients with rheumatoid arthritis (RA) may have great importance for optimising drug doses required for clinical benefit without toxicity. In a group of 125 RA patients treated with MTX we investigated whether selected polymorphisms in genes relevant for MTX action (aminoimidazole-4-carboxiamide ribonucleotide transformylase, ATIC, and dihydrofolate reductase, DHFR) modulate disease activity and/or have impact on therapy side effects. Methods The efficacy of treatment was estimated both by the disease activity score in 28 joints (DAS28), based on EULAR criteria, and relative DAS28 (rDAS28) score. Adverse drug events (ADEs) were also recorded. RA patients were genotyped using the PCR-RFLP method, followed by an association study between ATIC -129T>G, DHFR -216T>C and DHFR -317A>G polymorphisms and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 96 RA patients (76.8%) were classified as responders (good/moderate response) and 29 (23.2%) as non-responders (poor response). rDAS28 values ranged from -0.01 to 0.80 (mean value 0.31 +/- 0.19). Among 125 patients enrolled in this study 39 experienced at least one side effect. The DHFR -317AA genotype was associated with the less favourable response (reduction in rDAS28 score, p=0.05). None of the analysed polymorphisms was associated with MTX toxicity. Conclusion RA patients with DHFR-317AA genotype had less favourable response to MTX Further studies in larger patient populations are necessary to confirm the relationship between the analysed polymorphisms and MTX treatment response.",
publisher = "Clinical & Exper Rheumatology, Pisa",
journal = "Clinical & Experimental Rheumatology",
title = "Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis",
volume = "30",
number = "2",
pages = "178-183",
url = "https://hdl.handle.net/21.15107/rcub_smile_1741"
}
Milić, V., Jekić, B., Luković, L., Bunjevački, V., Milašin, J., Novaković, I., Damnjanović, T., Popović, B., Maksimović, N., Damjanov, N., Radunović, G., Pejnović, N.,& Krajinović, M.. (2012). Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis. in Clinical & Experimental Rheumatology
Clinical & Exper Rheumatology, Pisa., 30(2), 178-183.
https://hdl.handle.net/21.15107/rcub_smile_1741
Milić V, Jekić B, Luković L, Bunjevački V, Milašin J, Novaković I, Damnjanović T, Popović B, Maksimović N, Damjanov N, Radunović G, Pejnović N, Krajinović M. Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis. in Clinical & Experimental Rheumatology. 2012;30(2):178-183.
https://hdl.handle.net/21.15107/rcub_smile_1741 .
Milić, Vera, Jekić, Biljana, Luković, Ljiljana, Bunjevački, Vera, Milašin, Jelena, Novaković, I., Damnjanović, Tatjana, Popović, Branka, Maksimović, Nela, Damjanov, Nemanja, Radunović, Goran, Pejnović, Nada, Krajinović, Maja, "Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis" in Clinical & Experimental Rheumatology, 30, no. 2 (2012):178-183,
https://hdl.handle.net/21.15107/rcub_smile_1741 .
21

NPM1 gene mutations in children with Myelodysplastic syndromes

Jekić, Biljana; Bunjevački, Vera; Dobričić, Valerija; Novaković, Ivana; Milašin, Jelena; Popović, Branka; Damnjanović, Tatjana; Maksimović, Nela; Perović, V.; Luković, Ljiljana

(Srpsko biološko društvo, Beograd, i dr., 2011)

TY  - JOUR
AU  - Jekić, Biljana
AU  - Bunjevački, Vera
AU  - Dobričić, Valerija
AU  - Novaković, Ivana
AU  - Milašin, Jelena
AU  - Popović, Branka
AU  - Damnjanović, Tatjana
AU  - Maksimović, Nela
AU  - Perović, V.
AU  - Luković, Ljiljana
PY  - 2011
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1635
AB  - Myelodysplastic syndromes (MDS) are rare in children and only a few studies have analyzed their molecular mechanisms. The NPM1 gene encodes for nucleophosmin (NPM) which regulates hematopoiesis. Mutations in exon 12 of the NPM1 cause the nucleophosmin cytoplasmic dislocation and disrupt its functions. We have analyzed mutations of the NPM1 gene in archival bone marrow samples from 17 children with MDS and detected, in one patient, transition C to T in codon 293. To the best of our knowledge, this is the first analysis of NPM1 mutations in childhood MDS and the very first missense mutation of the NPM1 gene reported so far.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - NPM1 gene mutations in children with Myelodysplastic syndromes
VL  - 63
IS  - 3
SP  - 649
EP  - 653
DO  - 10.2298/ABS1103649J
ER  - 
@article{
author = "Jekić, Biljana and Bunjevački, Vera and Dobričić, Valerija and Novaković, Ivana and Milašin, Jelena and Popović, Branka and Damnjanović, Tatjana and Maksimović, Nela and Perović, V. and Luković, Ljiljana",
year = "2011",
abstract = "Myelodysplastic syndromes (MDS) are rare in children and only a few studies have analyzed their molecular mechanisms. The NPM1 gene encodes for nucleophosmin (NPM) which regulates hematopoiesis. Mutations in exon 12 of the NPM1 cause the nucleophosmin cytoplasmic dislocation and disrupt its functions. We have analyzed mutations of the NPM1 gene in archival bone marrow samples from 17 children with MDS and detected, in one patient, transition C to T in codon 293. To the best of our knowledge, this is the first analysis of NPM1 mutations in childhood MDS and the very first missense mutation of the NPM1 gene reported so far.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "NPM1 gene mutations in children with Myelodysplastic syndromes",
volume = "63",
number = "3",
pages = "649-653",
doi = "10.2298/ABS1103649J"
}
Jekić, B., Bunjevački, V., Dobričić, V., Novaković, I., Milašin, J., Popović, B., Damnjanović, T., Maksimović, N., Perović, V.,& Luković, L.. (2011). NPM1 gene mutations in children with Myelodysplastic syndromes. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 63(3), 649-653.
https://doi.org/10.2298/ABS1103649J
Jekić B, Bunjevački V, Dobričić V, Novaković I, Milašin J, Popović B, Damnjanović T, Maksimović N, Perović V, Luković L. NPM1 gene mutations in children with Myelodysplastic syndromes. in Archives of Biological Sciences. 2011;63(3):649-653.
doi:10.2298/ABS1103649J .
Jekić, Biljana, Bunjevački, Vera, Dobričić, Valerija, Novaković, Ivana, Milašin, Jelena, Popović, Branka, Damnjanović, Tatjana, Maksimović, Nela, Perović, V., Luković, Ljiljana, "NPM1 gene mutations in children with Myelodysplastic syndromes" in Archives of Biological Sciences, 63, no. 3 (2011):649-653,
https://doi.org/10.2298/ABS1103649J . .
1
1
2

Cancer genes alterations and HPV infection in oral squamous cell carcinoma

Popović, Branka; Jekić, Biljana; Novaković, Ivana; Luković, Ljiljana; Konstantinović, Vitomir; Babić, Marko; Milašin, Jelena

(Churchill Livingstone, Edinburgh, 2010)

TY  - JOUR
AU  - Popović, Branka
AU  - Jekić, Biljana
AU  - Novaković, Ivana
AU  - Luković, Ljiljana
AU  - Konstantinović, Vitomir
AU  - Babić, Marko
AU  - Milašin, Jelena
PY  - 2010
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1564
AB  - The aim of this study was to gain a better understanding of cancer genes contributing to oral squamous cell (OSCC) development and progression and correlate genetic changes to clinical parameters. Human papilloma virus (HPV) 16 detection is also included in the study. 60 samples of OSCC were analysed for erbB2 and c-myc amplification by dPCR, H-ras and p53 point mutations by PCR/SSCP. HPV was detected via amplification of its El and E6 genes. c-erbB2 was altered in 45%, c-myc in 35%, H-ras in 22% and p53 in 60% of samples. HPV was detected in 10% of cases. The frequency of p53 gene mutations showed a statistically significant association with tumour stage. Patients with c-erbB2 and H-ras alterations had lower survival than patients without these alterations. The number of detected genetic changes was remarkable but statistical association with tumour natural history was poor, indicating high clonal heterogeneity and multiple pathways of carcinogenesis.
PB  - Churchill Livingstone, Edinburgh
T2  - International Journal of Oral & Maxillofacial Surgery
T1  - Cancer genes alterations and HPV infection in oral squamous cell carcinoma
VL  - 39
IS  - 9
SP  - 909
EP  - 915
DO  - 10.1016/j.ijom.2010.05.007
ER  - 
@article{
author = "Popović, Branka and Jekić, Biljana and Novaković, Ivana and Luković, Ljiljana and Konstantinović, Vitomir and Babić, Marko and Milašin, Jelena",
year = "2010",
abstract = "The aim of this study was to gain a better understanding of cancer genes contributing to oral squamous cell (OSCC) development and progression and correlate genetic changes to clinical parameters. Human papilloma virus (HPV) 16 detection is also included in the study. 60 samples of OSCC were analysed for erbB2 and c-myc amplification by dPCR, H-ras and p53 point mutations by PCR/SSCP. HPV was detected via amplification of its El and E6 genes. c-erbB2 was altered in 45%, c-myc in 35%, H-ras in 22% and p53 in 60% of samples. HPV was detected in 10% of cases. The frequency of p53 gene mutations showed a statistically significant association with tumour stage. Patients with c-erbB2 and H-ras alterations had lower survival than patients without these alterations. The number of detected genetic changes was remarkable but statistical association with tumour natural history was poor, indicating high clonal heterogeneity and multiple pathways of carcinogenesis.",
publisher = "Churchill Livingstone, Edinburgh",
journal = "International Journal of Oral & Maxillofacial Surgery",
title = "Cancer genes alterations and HPV infection in oral squamous cell carcinoma",
volume = "39",
number = "9",
pages = "909-915",
doi = "10.1016/j.ijom.2010.05.007"
}
Popović, B., Jekić, B., Novaković, I., Luković, L., Konstantinović, V., Babić, M.,& Milašin, J.. (2010). Cancer genes alterations and HPV infection in oral squamous cell carcinoma. in International Journal of Oral & Maxillofacial Surgery
Churchill Livingstone, Edinburgh., 39(9), 909-915.
https://doi.org/10.1016/j.ijom.2010.05.007
Popović B, Jekić B, Novaković I, Luković L, Konstantinović V, Babić M, Milašin J. Cancer genes alterations and HPV infection in oral squamous cell carcinoma. in International Journal of Oral & Maxillofacial Surgery. 2010;39(9):909-915.
doi:10.1016/j.ijom.2010.05.007 .
Popović, Branka, Jekić, Biljana, Novaković, Ivana, Luković, Ljiljana, Konstantinović, Vitomir, Babić, Marko, Milašin, Jelena, "Cancer genes alterations and HPV infection in oral squamous cell carcinoma" in International Journal of Oral & Maxillofacial Surgery, 39, no. 9 (2010):909-915,
https://doi.org/10.1016/j.ijom.2010.05.007 . .
23
19
25

Association Between the Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia in Serbian Children

Damnjanović, Tatjana; Milicević, Radomir; Novković, Tanja; Jovičić, Olivera; Bunjevački, Vera; Jekić, Biljana; Luković, Ljiljana; Novaković, Ivana; Redzić, Danka; Milašin, Jelena

(Lippincott Williams & Wilkins, Philadelphia, 2010)

TY  - JOUR
AU  - Damnjanović, Tatjana
AU  - Milicević, Radomir
AU  - Novković, Tanja
AU  - Jovičić, Olivera
AU  - Bunjevački, Vera
AU  - Jekić, Biljana
AU  - Luković, Ljiljana
AU  - Novaković, Ivana
AU  - Redzić, Danka
AU  - Milašin, Jelena
PY  - 2010
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1582
AB  - Methylenetetrahydrofolate reductase (MTHFR) regulates the metabolism of folate and methionine, essential components of DNA synthesis and methylation. Polymorphisms in the MTHFR gene have been associated with susceptibility to some types of cancer. We investigated a possible association of MTHFR polymorphisms (677C > T and 1298A > C) and increased risk for acute lymphoblastic leukemia in 78 affected children. The frequencies of both MTHFR 677 genotypes and alleles were significantly different between patients and controls. A significant association between CT/TT individuals and reduced risk of acute lymphoblastic leukemia was found. The odds ratios were 0.53 (95% confidence interval, 032-0.89) and 0.30 (95% confidence interval, 0.12-0.81). Polymorphism 1298 did not show statistical difference between patients and controls.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Journal of Pediatric Hematology Oncology
T1  - Association Between the Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia in Serbian Children
VL  - 32
IS  - 4
SP  - E148
EP  - E150
DO  - 10.1097/MPH.0b013e3181cbd252
ER  - 
@article{
author = "Damnjanović, Tatjana and Milicević, Radomir and Novković, Tanja and Jovičić, Olivera and Bunjevački, Vera and Jekić, Biljana and Luković, Ljiljana and Novaković, Ivana and Redzić, Danka and Milašin, Jelena",
year = "2010",
abstract = "Methylenetetrahydrofolate reductase (MTHFR) regulates the metabolism of folate and methionine, essential components of DNA synthesis and methylation. Polymorphisms in the MTHFR gene have been associated with susceptibility to some types of cancer. We investigated a possible association of MTHFR polymorphisms (677C > T and 1298A > C) and increased risk for acute lymphoblastic leukemia in 78 affected children. The frequencies of both MTHFR 677 genotypes and alleles were significantly different between patients and controls. A significant association between CT/TT individuals and reduced risk of acute lymphoblastic leukemia was found. The odds ratios were 0.53 (95% confidence interval, 032-0.89) and 0.30 (95% confidence interval, 0.12-0.81). Polymorphism 1298 did not show statistical difference between patients and controls.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Journal of Pediatric Hematology Oncology",
title = "Association Between the Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia in Serbian Children",
volume = "32",
number = "4",
pages = "E148-E150",
doi = "10.1097/MPH.0b013e3181cbd252"
}
Damnjanović, T., Milicević, R., Novković, T., Jovičić, O., Bunjevački, V., Jekić, B., Luković, L., Novaković, I., Redzić, D.,& Milašin, J.. (2010). Association Between the Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia in Serbian Children. in Journal of Pediatric Hematology Oncology
Lippincott Williams & Wilkins, Philadelphia., 32(4), E148-E150.
https://doi.org/10.1097/MPH.0b013e3181cbd252
Damnjanović T, Milicević R, Novković T, Jovičić O, Bunjevački V, Jekić B, Luković L, Novaković I, Redzić D, Milašin J. Association Between the Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia in Serbian Children. in Journal of Pediatric Hematology Oncology. 2010;32(4):E148-E150.
doi:10.1097/MPH.0b013e3181cbd252 .
Damnjanović, Tatjana, Milicević, Radomir, Novković, Tanja, Jovičić, Olivera, Bunjevački, Vera, Jekić, Biljana, Luković, Ljiljana, Novaković, Ivana, Redzić, Danka, Milašin, Jelena, "Association Between the Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia in Serbian Children" in Journal of Pediatric Hematology Oncology, 32, no. 4 (2010):E148-E150,
https://doi.org/10.1097/MPH.0b013e3181cbd252 . .
21
20
21

Mutation status of p53 gene in oral squamous cell carcinoma

Popović, Branka; Jekić, Biljana; Jelovac, Drago; Novaković, Ivana

(Srpsko lekarsko društvo - Stomatološka sekcija, Beograd, 2009)

TY  - JOUR
AU  - Popović, Branka
AU  - Jekić, Biljana
AU  - Jelovac, Drago
AU  - Novaković, Ivana
PY  - 2009
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1470
AB  - Introduction. p53 gene is the most common tumor suppressor gene involved in pathogenesis oral squamous cell carcinoma (OSCC). Protein product of p53 gene contributes to cell cycle control and apoptosis. p53 gene mutations may lead to uncontrolled cell growth. The aim of this study was to determine the incidence of mutation in DNA-binding domain of p53 gene. Materials and Methods. In the 60 specimens, the presence of point mutation in exons 5, 6, 7 and 8 was detected using PCR-SSCP method. To confirm the presence of p53 mutation found by SSCP method, five samples were analyzed by sequencing of exon 5. Results. Point mutation affecting exons 5, 6, 7 and 8 were found in 60% of analyzed samples. A higher incidence of mutation was detected in exon 7 and 8 (60%), than in exon 5 and 6. Sequencing of exon 5, confirmed the presence of mutations revealed by SSCP method. Study of associations showed an increase of p53 mutations in poor differentiated and carcinoma of higher clinical stages. Conclusion. p53 gene is one of major factor in control of cell cycle and has important role in pathogenesis of oral squamous cell carcinoma.
AB  - Uvod. TP53 je ključni tumor-supresorski gen uključen u patogenezu oralnih skvamocelularnih karcinoma (OSCK). Proteinski proizvod gena p53 zadužen je za kontrolu ćelijskog ciklusa i apoptozu, a mutacije u TP53 mogu dovesti do nekontrolisane proliferacije ćelija. Cilj ovog rada je bio da se utvrdi zastupljenost tačkastih mutacija u regionu gena p53 koji se vezuje za DNK, odnosno proceni uloga ovoga gena u patogenezi OSCK. Materijal i metode rada. U 60 uzoraka OSCK su korišćenjem metode lančane reakcije polimeraze i polimorfizma jednolančanih fragmenata DNK (PCR-SSCP) ispitane tačkaste mutacije u egzonima 5, 6, 7 i 8 gena p53. Pet slučajno odabranih uzoraka u kojima je otkrivena mutacija naknadno je podvrgnuto sekvenciranju radi potvrde validnosti metode PCR-SSCP. Rezultati. Tačkaste mutacije u nekom od analiziranih egzona gena p53 utvrđene su u 60% uzoraka OSCK. Veća učestalost mutacija zabeležena je u egzonima 7 i 8. Sekvenciranje je potvrdilo mutacije otkrivene metodom SSCP. Studija asocijacije pokazuje povećanje broja mutacija gena p53 kod slabo diferenciranih i karcinoma viših kliničkih stadijuma. Zaključak. Gen p53, jedan od glavnih kontrolora ćelijskog ciklusa, ima značajnu ulogu i u patogenezi karcinoma oralne duplje.
PB  - Srpsko lekarsko društvo - Stomatološka sekcija, Beograd
T2  - Stomatološki glasnik Srbije
T1  - Mutation status of p53 gene in oral squamous cell carcinoma
T1  - Mutacioni status gena p53 u oralnim skvamocelularnim karcinomima
VL  - 56
IS  - 4
SP  - 171
EP  - 175
DO  - 10.2298/SGS0904171P
ER  - 
@article{
author = "Popović, Branka and Jekić, Biljana and Jelovac, Drago and Novaković, Ivana",
year = "2009",
abstract = "Introduction. p53 gene is the most common tumor suppressor gene involved in pathogenesis oral squamous cell carcinoma (OSCC). Protein product of p53 gene contributes to cell cycle control and apoptosis. p53 gene mutations may lead to uncontrolled cell growth. The aim of this study was to determine the incidence of mutation in DNA-binding domain of p53 gene. Materials and Methods. In the 60 specimens, the presence of point mutation in exons 5, 6, 7 and 8 was detected using PCR-SSCP method. To confirm the presence of p53 mutation found by SSCP method, five samples were analyzed by sequencing of exon 5. Results. Point mutation affecting exons 5, 6, 7 and 8 were found in 60% of analyzed samples. A higher incidence of mutation was detected in exon 7 and 8 (60%), than in exon 5 and 6. Sequencing of exon 5, confirmed the presence of mutations revealed by SSCP method. Study of associations showed an increase of p53 mutations in poor differentiated and carcinoma of higher clinical stages. Conclusion. p53 gene is one of major factor in control of cell cycle and has important role in pathogenesis of oral squamous cell carcinoma., Uvod. TP53 je ključni tumor-supresorski gen uključen u patogenezu oralnih skvamocelularnih karcinoma (OSCK). Proteinski proizvod gena p53 zadužen je za kontrolu ćelijskog ciklusa i apoptozu, a mutacije u TP53 mogu dovesti do nekontrolisane proliferacije ćelija. Cilj ovog rada je bio da se utvrdi zastupljenost tačkastih mutacija u regionu gena p53 koji se vezuje za DNK, odnosno proceni uloga ovoga gena u patogenezi OSCK. Materijal i metode rada. U 60 uzoraka OSCK su korišćenjem metode lančane reakcije polimeraze i polimorfizma jednolančanih fragmenata DNK (PCR-SSCP) ispitane tačkaste mutacije u egzonima 5, 6, 7 i 8 gena p53. Pet slučajno odabranih uzoraka u kojima je otkrivena mutacija naknadno je podvrgnuto sekvenciranju radi potvrde validnosti metode PCR-SSCP. Rezultati. Tačkaste mutacije u nekom od analiziranih egzona gena p53 utvrđene su u 60% uzoraka OSCK. Veća učestalost mutacija zabeležena je u egzonima 7 i 8. Sekvenciranje je potvrdilo mutacije otkrivene metodom SSCP. Studija asocijacije pokazuje povećanje broja mutacija gena p53 kod slabo diferenciranih i karcinoma viših kliničkih stadijuma. Zaključak. Gen p53, jedan od glavnih kontrolora ćelijskog ciklusa, ima značajnu ulogu i u patogenezi karcinoma oralne duplje.",
publisher = "Srpsko lekarsko društvo - Stomatološka sekcija, Beograd",
journal = "Stomatološki glasnik Srbije",
title = "Mutation status of p53 gene in oral squamous cell carcinoma, Mutacioni status gena p53 u oralnim skvamocelularnim karcinomima",
volume = "56",
number = "4",
pages = "171-175",
doi = "10.2298/SGS0904171P"
}
Popović, B., Jekić, B., Jelovac, D.,& Novaković, I.. (2009). Mutation status of p53 gene in oral squamous cell carcinoma. in Stomatološki glasnik Srbije
Srpsko lekarsko društvo - Stomatološka sekcija, Beograd., 56(4), 171-175.
https://doi.org/10.2298/SGS0904171P
Popović B, Jekić B, Jelovac D, Novaković I. Mutation status of p53 gene in oral squamous cell carcinoma. in Stomatološki glasnik Srbije. 2009;56(4):171-175.
doi:10.2298/SGS0904171P .
Popović, Branka, Jekić, Biljana, Jelovac, Drago, Novaković, Ivana, "Mutation status of p53 gene in oral squamous cell carcinoma" in Stomatološki glasnik Srbije, 56, no. 4 (2009):171-175,
https://doi.org/10.2298/SGS0904171P . .
1

Analysis of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma

Popović, Branka; Jekić, Biljana; Novaković, Ivana; Milašin, Jelena

(Srpsko lekarsko društvo - Stomatološka sekcija, Beograd, 2007)

TY  - JOUR
AU  - Popović, Branka
AU  - Jekić, Biljana
AU  - Novaković, Ivana
AU  - Milašin, Jelena
PY  - 2007
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1371
AB  - Aim: The aim of this study was to analyze the presence of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma and determine its potential role in the development and progression of this type of tumor. Materials and methods: The expression of bcl-2 was determined in 28 paraffin blocks of oral squamous cell carcinoma using the immunohistochemical method. The percentage of the immuno-reactive cells in positively stained tumor regions was determined using the microscopic analysis and Ozaria software. Results: Positive immunohistochemical test was observed in 19 out of 28 samples (68%) as follows: in 11 samples there was a low (+), in four a moderate (++) and in the last four a high percentage (+++) of stained cells. In the group of patients at the low stage of the disease (T2), 50% of tumor samples showed bcl-2 protein expression whereas in the higher stages (T3 and T4) of positively stained samples, this percentage was 67%. There was a trend of an increasing number of cells with positive bcl-2 staining in the tumors of higher clinical stages but not the level of bcl-2 protein expression. Conclusion: Both parameters, the presence of bcl-2 staining and the percentage of cells with bcl-2 immunoexpression, may act as additional prognostic parameters that indicate an increased proliferative tumor potential.
AB  - Cilj ove studije bio je analiza prisustva antiapoptotskog proteina bcl-2 u skvamocelularnom karcinomu usne regije i procena njegove eventualne uloge u razvoju i progresiji ove vrste tumora. Materijal i metode: Na uzorku od 28 parafinskih blokova skvamocelularnog karcinoma usne regije, imunohistohemijskom metodom ispitan je ekspresioni status bcl-2 proteina. Mikroskopskom analizom i primenom softvera- Ozaria određen je procenat imunoreaktivnih ćelija u pozitivno obojenim tumorskim regijama. Rezultat: Pozitivnu imunohistohemijsku obojenost pokazalo je 19 od 28 uzoraka (68%) i to: 11 je bilo sa niskim (+), 4 sa srednjim (++) i 4 sa visokim procentom (+++) obojenih ćelija. U grupi pacijenata niskog stadijuma (T2) 50 % uzoraka tumora je pokazivalo ekspresiju bcl-2 proteina dok je u višim stadijumima (T3 i T4) pozitivnih uzoraka bilo 67%. Postojao je trend porasta broja ćelija sa pozitivnom bcl-2 obojenošću kod tumora u višim kliničkim stadijumima, ali ne i povećan nivo ekspresije bcl-2 proteina. Zaključak: Oba parametra, prisustvo bcl-2 obojenosti i procenat ćelija sa bcl-2 imunoekspresijom, mogu predstavljati dopunske prognostičke parametre koji ukazuju na povećan proliferativni potencijal tumora.
PB  - Srpsko lekarsko društvo - Stomatološka sekcija, Beograd
T2  - Stomatološki glasnik Srbije
T1  - Analysis of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma
T1  - Analiza antiapoptotskog proteina bcl-2 u skvamocelularnom karcinomu usne regije
VL  - 54
IS  - 3
SP  - 153
EP  - 159
DO  - 10.2298/SGS0703153P
ER  - 
@article{
author = "Popović, Branka and Jekić, Biljana and Novaković, Ivana and Milašin, Jelena",
year = "2007",
abstract = "Aim: The aim of this study was to analyze the presence of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma and determine its potential role in the development and progression of this type of tumor. Materials and methods: The expression of bcl-2 was determined in 28 paraffin blocks of oral squamous cell carcinoma using the immunohistochemical method. The percentage of the immuno-reactive cells in positively stained tumor regions was determined using the microscopic analysis and Ozaria software. Results: Positive immunohistochemical test was observed in 19 out of 28 samples (68%) as follows: in 11 samples there was a low (+), in four a moderate (++) and in the last four a high percentage (+++) of stained cells. In the group of patients at the low stage of the disease (T2), 50% of tumor samples showed bcl-2 protein expression whereas in the higher stages (T3 and T4) of positively stained samples, this percentage was 67%. There was a trend of an increasing number of cells with positive bcl-2 staining in the tumors of higher clinical stages but not the level of bcl-2 protein expression. Conclusion: Both parameters, the presence of bcl-2 staining and the percentage of cells with bcl-2 immunoexpression, may act as additional prognostic parameters that indicate an increased proliferative tumor potential., Cilj ove studije bio je analiza prisustva antiapoptotskog proteina bcl-2 u skvamocelularnom karcinomu usne regije i procena njegove eventualne uloge u razvoju i progresiji ove vrste tumora. Materijal i metode: Na uzorku od 28 parafinskih blokova skvamocelularnog karcinoma usne regije, imunohistohemijskom metodom ispitan je ekspresioni status bcl-2 proteina. Mikroskopskom analizom i primenom softvera- Ozaria određen je procenat imunoreaktivnih ćelija u pozitivno obojenim tumorskim regijama. Rezultat: Pozitivnu imunohistohemijsku obojenost pokazalo je 19 od 28 uzoraka (68%) i to: 11 je bilo sa niskim (+), 4 sa srednjim (++) i 4 sa visokim procentom (+++) obojenih ćelija. U grupi pacijenata niskog stadijuma (T2) 50 % uzoraka tumora je pokazivalo ekspresiju bcl-2 proteina dok je u višim stadijumima (T3 i T4) pozitivnih uzoraka bilo 67%. Postojao je trend porasta broja ćelija sa pozitivnom bcl-2 obojenošću kod tumora u višim kliničkim stadijumima, ali ne i povećan nivo ekspresije bcl-2 proteina. Zaključak: Oba parametra, prisustvo bcl-2 obojenosti i procenat ćelija sa bcl-2 imunoekspresijom, mogu predstavljati dopunske prognostičke parametre koji ukazuju na povećan proliferativni potencijal tumora.",
publisher = "Srpsko lekarsko društvo - Stomatološka sekcija, Beograd",
journal = "Stomatološki glasnik Srbije",
title = "Analysis of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma, Analiza antiapoptotskog proteina bcl-2 u skvamocelularnom karcinomu usne regije",
volume = "54",
number = "3",
pages = "153-159",
doi = "10.2298/SGS0703153P"
}
Popović, B., Jekić, B., Novaković, I.,& Milašin, J.. (2007). Analysis of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma. in Stomatološki glasnik Srbije
Srpsko lekarsko društvo - Stomatološka sekcija, Beograd., 54(3), 153-159.
https://doi.org/10.2298/SGS0703153P
Popović B, Jekić B, Novaković I, Milašin J. Analysis of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma. in Stomatološki glasnik Srbije. 2007;54(3):153-159.
doi:10.2298/SGS0703153P .
Popović, Branka, Jekić, Biljana, Novaković, Ivana, Milašin, Jelena, "Analysis of the anti-apoptotic protein bcl-2 in oral squamous cell carcinoma" in Stomatološki glasnik Srbije, 54, no. 3 (2007):153-159,
https://doi.org/10.2298/SGS0703153P . .

LeX chromosome imprinting in turner syndrome

Damnjanović, Tatjana; Novaković, Ivana; Milašin, Jelena; Bunjevački, Vera; Jekić, Biljana; Cvijeticanin, Suzana; Luković, Ljiljana

(2007)

TY  - JOUR
AU  - Damnjanović, Tatjana
AU  - Novaković, Ivana
AU  - Milašin, Jelena
AU  - Bunjevački, Vera
AU  - Jekić, Biljana
AU  - Cvijeticanin, Suzana
AU  - Luković, Ljiljana
PY  - 2007
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1365
AB  - The objective of this study was to assess indirectly the existence of X imprinting and its potential role in a number of clinical characteristics of Turner syndrome patients. Highly polymorphic X linked microsatellite markers were used to determine the origin of the single X chromosome in 13 patients with Turner syndrome. Ten (77%) patients retained the maternal X chromosome (X-m), while only three patients (23%) retained the paternal X chromosome (X-p). Fisher exact statistical test was used for the association of X chromosome origin with the clinical phenotype. No significant difference was found between the two groups of patients regarding the following phenotype characteristics: lymphoedema. at birth, short neck, low posterior hairline, eye anomalies (ptosis, epicanthal folds, hypertelorism, strabismus), multiple pigmented naevi, cardiac and renal anomalies. Absence association between the X chromosome origin and Turner phenotype was confirmed by a meta-analysis combining five studies, including this one. It was only neck webbing that showed a trend of association with X-m.
T2  - Korean Journal of Genetics
T1  - LeX chromosome imprinting in turner syndrome
VL  - 29
IS  - 3
SP  - 291
EP  - 295
UR  - https://hdl.handle.net/21.15107/rcub_smile_1365
ER  - 
@article{
author = "Damnjanović, Tatjana and Novaković, Ivana and Milašin, Jelena and Bunjevački, Vera and Jekić, Biljana and Cvijeticanin, Suzana and Luković, Ljiljana",
year = "2007",
abstract = "The objective of this study was to assess indirectly the existence of X imprinting and its potential role in a number of clinical characteristics of Turner syndrome patients. Highly polymorphic X linked microsatellite markers were used to determine the origin of the single X chromosome in 13 patients with Turner syndrome. Ten (77%) patients retained the maternal X chromosome (X-m), while only three patients (23%) retained the paternal X chromosome (X-p). Fisher exact statistical test was used for the association of X chromosome origin with the clinical phenotype. No significant difference was found between the two groups of patients regarding the following phenotype characteristics: lymphoedema. at birth, short neck, low posterior hairline, eye anomalies (ptosis, epicanthal folds, hypertelorism, strabismus), multiple pigmented naevi, cardiac and renal anomalies. Absence association between the X chromosome origin and Turner phenotype was confirmed by a meta-analysis combining five studies, including this one. It was only neck webbing that showed a trend of association with X-m.",
journal = "Korean Journal of Genetics",
title = "LeX chromosome imprinting in turner syndrome",
volume = "29",
number = "3",
pages = "291-295",
url = "https://hdl.handle.net/21.15107/rcub_smile_1365"
}
Damnjanović, T., Novaković, I., Milašin, J., Bunjevački, V., Jekić, B., Cvijeticanin, S.,& Luković, L.. (2007). LeX chromosome imprinting in turner syndrome. in Korean Journal of Genetics, 29(3), 291-295.
https://hdl.handle.net/21.15107/rcub_smile_1365
Damnjanović T, Novaković I, Milašin J, Bunjevački V, Jekić B, Cvijeticanin S, Luković L. LeX chromosome imprinting in turner syndrome. in Korean Journal of Genetics. 2007;29(3):291-295.
https://hdl.handle.net/21.15107/rcub_smile_1365 .
Damnjanović, Tatjana, Novaković, Ivana, Milašin, Jelena, Bunjevački, Vera, Jekić, Biljana, Cvijeticanin, Suzana, Luković, Ljiljana, "LeX chromosome imprinting in turner syndrome" in Korean Journal of Genetics, 29, no. 3 (2007):291-295,
https://hdl.handle.net/21.15107/rcub_smile_1365 .
1
1

The application of genetic modifications in gene therapy and pharmacological investigations in the medicine

Novaković, Ivana; Jekić, Biljana; Milašin, Jelena

(Savez poljoprivrednih inženjera i tehničara, Beograd, 2005)

TY  - JOUR
AU  - Novaković, Ivana
AU  - Jekić, Biljana
AU  - Milašin, Jelena
PY  - 2005
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1265
AB  - In the broadest sense of the word gene therapy is any exogenous influence on gene activity. However this term is frequently used for treatment of disease by introduction of genetic material (genes, parts of genes, antisense olygonucleotides etc) in the patient's tissue. At this moment the possibilities of gene therapies are restricted on treatment of somatic cells only. One of the important criteria for choice of disease that will be treated is absence of other useful therapy, so majority of protocols are for malignant diseases, than for serious monogenic disorders (cystic fibrosis Duchenne muscular dystrophy), AIDS etc. Depending on effects we want, basic strategies for gene therapy are gene augmentation on inhibition of expression, targeted killing of specific cells or gene replacement. For transfer of genetic material viral or non-viral vectors could be used, as well as biolystic techniques with gene guns or direct injection of genetic material in tissue. Application of gene therapy still has several technical problems, but severe side effects are also possible, such as infections by viral vectors or activation of malignant transformation by unpredictable place of insertion of genetic material. Regardless of all difficulties we expect that gene therapy will become part of standard medical practice in the near feature. Manipulations with genetic material have also wild implementation in the experimental work in biomedicine. In our investigation in the area of experimental cardiovascular pharmacology, we will use adenoviral vectors unable for replication carrying oxytocin and vasopressin receptors genes.
AB  - Genska terapija u širem smislu je svaki egzogeni - spoljašnji uticaj na aktivnost određenih gena. Uža i najčešće primenjivana definicija genske terapije podrazumeva tretman bolesti unošenjem genetičkog materijala (geni delovi gena, antisens oligonukleotidi itd) u ciljno tkivo pacijenta. U ovom trenutku genske terapije su ograničene isključivo na telesne tj. somatske ćelije. U izboru bolesti koja će se tretirati genskom terapijom važan kriterijum je da ne postoji drugi efikasan način lečenja, pa se najveći broj protokola odnosi na maligna oboljenja, a potom na teške monogenske bolesti (cistična fibroza, Dišenova mišićna distrofija), SID-u itd. U zavisnosti od željenog efekta postoji nekoliko osnovnih strategija genske terapije pojačanje dejstva gena ili pak inhibicija njegove ekspresije, ciljano ubijanje specifičnih ćelija ili zamena gena. Za prenos genetičkog materijala se koriste virusi ali i neviralni vektori (npr. lipozomi), biolističke tehnike sa primenom "genskog pištolja" ili čak direktno injektiranje genetičkog materijala u tkivo. Pored još uvek brojnih tehničkih ograničenja genska terapija nosi sa sobom probleme vezane za neželjene efekte, kao što su teške infekcije kod korišćenja virusnih vektora, ili pokretanje maligne transformacije usled slučajnog mesta ugradnje unetog genetičkog materijala. Bez obzira na sve poteškoće, očekuje se da će u skoroj budućnosti primena lečenja genima postati deo uobičajene medicinske prakse. Manipulacije genetičkim materijalom i se široko primenjuju i u eksperimentalnom radu u biomedicini. U našem istraživanju iz oblasti kardiovaskularne farmakologije za ispitivanje nonkcije oksitocina i vazopresina konstruisaćemo replikaciono nesposobne adenovirusne vektore koji će nositi gene za receptore za vazopresin i oksitocin.
PB  - Savez poljoprivrednih inženjera i tehničara, Beograd
T2  - Journal of Scientific Agricultural Research
T1  - The application of genetic modifications in gene therapy and pharmacological investigations in the medicine
T1  - Primena genetičkih modifikacija u genskoj terapiji i farmakološkim ispitivanjima u medicini
VL  - 66
IS  - 5
SP  - 223
EP  - 228
UR  - https://hdl.handle.net/21.15107/rcub_smile_1265
ER  - 
@article{
author = "Novaković, Ivana and Jekić, Biljana and Milašin, Jelena",
year = "2005",
abstract = "In the broadest sense of the word gene therapy is any exogenous influence on gene activity. However this term is frequently used for treatment of disease by introduction of genetic material (genes, parts of genes, antisense olygonucleotides etc) in the patient's tissue. At this moment the possibilities of gene therapies are restricted on treatment of somatic cells only. One of the important criteria for choice of disease that will be treated is absence of other useful therapy, so majority of protocols are for malignant diseases, than for serious monogenic disorders (cystic fibrosis Duchenne muscular dystrophy), AIDS etc. Depending on effects we want, basic strategies for gene therapy are gene augmentation on inhibition of expression, targeted killing of specific cells or gene replacement. For transfer of genetic material viral or non-viral vectors could be used, as well as biolystic techniques with gene guns or direct injection of genetic material in tissue. Application of gene therapy still has several technical problems, but severe side effects are also possible, such as infections by viral vectors or activation of malignant transformation by unpredictable place of insertion of genetic material. Regardless of all difficulties we expect that gene therapy will become part of standard medical practice in the near feature. Manipulations with genetic material have also wild implementation in the experimental work in biomedicine. In our investigation in the area of experimental cardiovascular pharmacology, we will use adenoviral vectors unable for replication carrying oxytocin and vasopressin receptors genes., Genska terapija u širem smislu je svaki egzogeni - spoljašnji uticaj na aktivnost određenih gena. Uža i najčešće primenjivana definicija genske terapije podrazumeva tretman bolesti unošenjem genetičkog materijala (geni delovi gena, antisens oligonukleotidi itd) u ciljno tkivo pacijenta. U ovom trenutku genske terapije su ograničene isključivo na telesne tj. somatske ćelije. U izboru bolesti koja će se tretirati genskom terapijom važan kriterijum je da ne postoji drugi efikasan način lečenja, pa se najveći broj protokola odnosi na maligna oboljenja, a potom na teške monogenske bolesti (cistična fibroza, Dišenova mišićna distrofija), SID-u itd. U zavisnosti od željenog efekta postoji nekoliko osnovnih strategija genske terapije pojačanje dejstva gena ili pak inhibicija njegove ekspresije, ciljano ubijanje specifičnih ćelija ili zamena gena. Za prenos genetičkog materijala se koriste virusi ali i neviralni vektori (npr. lipozomi), biolističke tehnike sa primenom "genskog pištolja" ili čak direktno injektiranje genetičkog materijala u tkivo. Pored još uvek brojnih tehničkih ograničenja genska terapija nosi sa sobom probleme vezane za neželjene efekte, kao što su teške infekcije kod korišćenja virusnih vektora, ili pokretanje maligne transformacije usled slučajnog mesta ugradnje unetog genetičkog materijala. Bez obzira na sve poteškoće, očekuje se da će u skoroj budućnosti primena lečenja genima postati deo uobičajene medicinske prakse. Manipulacije genetičkim materijalom i se široko primenjuju i u eksperimentalnom radu u biomedicini. U našem istraživanju iz oblasti kardiovaskularne farmakologije za ispitivanje nonkcije oksitocina i vazopresina konstruisaćemo replikaciono nesposobne adenovirusne vektore koji će nositi gene za receptore za vazopresin i oksitocin.",
publisher = "Savez poljoprivrednih inženjera i tehničara, Beograd",
journal = "Journal of Scientific Agricultural Research",
title = "The application of genetic modifications in gene therapy and pharmacological investigations in the medicine, Primena genetičkih modifikacija u genskoj terapiji i farmakološkim ispitivanjima u medicini",
volume = "66",
number = "5",
pages = "223-228",
url = "https://hdl.handle.net/21.15107/rcub_smile_1265"
}
Novaković, I., Jekić, B.,& Milašin, J.. (2005). The application of genetic modifications in gene therapy and pharmacological investigations in the medicine. in Journal of Scientific Agricultural Research
Savez poljoprivrednih inženjera i tehničara, Beograd., 66(5), 223-228.
https://hdl.handle.net/21.15107/rcub_smile_1265
Novaković I, Jekić B, Milašin J. The application of genetic modifications in gene therapy and pharmacological investigations in the medicine. in Journal of Scientific Agricultural Research. 2005;66(5):223-228.
https://hdl.handle.net/21.15107/rcub_smile_1265 .
Novaković, Ivana, Jekić, Biljana, Milašin, Jelena, "The application of genetic modifications in gene therapy and pharmacological investigations in the medicine" in Journal of Scientific Agricultural Research, 66, no. 5 (2005):223-228,
https://hdl.handle.net/21.15107/rcub_smile_1265 .