TY  - JOUR
AU  - Nedeljković, Milica
AU  - Tanić, Nasta
AU  - Prvanović, Mirjana
AU  - Milovanović, Zorka
AU  - Tanić, Nikola
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9173
AB  - Background: ATP-binding cassette (ABC) transporters are responsible for the efflux of a wide variety of anti-cancer agents and have been implicated in the chemoresistance of various solid tumors. Chemoresistance is a major cause of therapeutic failure, especially in the highly aggressive triple-negative breast cancer (TNBC) in which, unlike estrogen receptor-expressing (ER+) BC, both endocrine and targeted treatments are ineffectual. We aimed to investigate the level and frequency of expression of the three most important ABC transporter, ABCG2, ABCC1, and ABCB1, according to breast cancer subtype. Methods: We evaluated ABCG2, ABCC1, and ABCB1 protein expressions in 124 primary breast tumors (78 samples were classified as TNBC, while 46 were classified as ER+) by immunohistochemistry and correlated it to clinicopathological characteristics and outcome. Results: All three transporters had significantly higher expression and were more frequently expressed in TNBC compared to ER+ tumors (p < 0.0001). ABCG2 and ABCC1 had a very high level of expression in TNBC that was significantly greater compared to ABCB1 (p < 0.0001). ABCB1 expression was associated with TNBC metastatic spread (p = 0.03). In contrast, TNBC patients with high ABCG2 expression level had significantly longer disease-free interval (p = 0.03) and overall survival (p = 0.007). Conclusion: ABCG2, ABCC1, and ABCB1 expression in breast cancer is subtype-specific and associated with triple-negative tumors. The expression of ABCB1 may be useful as a marker of metastatic spread. Moreover, unexpectedly, our results showed a beneficial effect of ABCG2 expression on TNBC clinical behavior. These findings could have implications for the implementation of future TNBC treatment strategies.
T2  - Breast Cancer
T1  - Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer
VL  - 28
IS  - 3
SP  - 727
EP  - 736
DO  - 10.1007/s12282-020-01210-z
ER  - 

@article{
author = "Nedeljković, Milica and Tanić, Nasta and Prvanović, Mirjana and Milovanović, Zorka and Tanić, Nikola",
year = "2021",
abstract = "Background: ATP-binding cassette (ABC) transporters are responsible for the efflux of a wide variety of anti-cancer agents and have been implicated in the chemoresistance of various solid tumors. Chemoresistance is a major cause of therapeutic failure, especially in the highly aggressive triple-negative breast cancer (TNBC) in which, unlike estrogen receptor-expressing (ER+) BC, both endocrine and targeted treatments are ineffectual. We aimed to investigate the level and frequency of expression of the three most important ABC transporter, ABCG2, ABCC1, and ABCB1, according to breast cancer subtype. Methods: We evaluated ABCG2, ABCC1, and ABCB1 protein expressions in 124 primary breast tumors (78 samples were classified as TNBC, while 46 were classified as ER+) by immunohistochemistry and correlated it to clinicopathological characteristics and outcome. Results: All three transporters had significantly higher expression and were more frequently expressed in TNBC compared to ER+ tumors (p < 0.0001). ABCG2 and ABCC1 had a very high level of expression in TNBC that was significantly greater compared to ABCB1 (p < 0.0001). ABCB1 expression was associated with TNBC metastatic spread (p = 0.03). In contrast, TNBC patients with high ABCG2 expression level had significantly longer disease-free interval (p = 0.03) and overall survival (p = 0.007). Conclusion: ABCG2, ABCC1, and ABCB1 expression in breast cancer is subtype-specific and associated with triple-negative tumors. The expression of ABCB1 may be useful as a marker of metastatic spread. Moreover, unexpectedly, our results showed a beneficial effect of ABCG2 expression on TNBC clinical behavior. These findings could have implications for the implementation of future TNBC treatment strategies.",
journal = "Breast Cancer",
title = "Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer",
volume = "28",
number = "3",
pages = "727-736",
doi = "10.1007/s12282-020-01210-z"
}

Nedeljković, M., Tanić, N., Prvanović, M., Milovanović, Z.,& Tanić, N.. (2021). Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer. in Breast Cancer, 28(3), 727-736.
https://doi.org/10.1007/s12282-020-01210-z

Nedeljković M, Tanić N, Prvanović M, Milovanović Z, Tanić N. Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer. in Breast Cancer. 2021;28(3):727-736.
doi:10.1007/s12282-020-01210-z .

Nedeljković, Milica, Tanić, Nasta, Prvanović, Mirjana, Milovanović, Zorka, Tanić, Nikola, "Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer" in Breast Cancer, 28, no. 3 (2021):727-736,
https://doi.org/10.1007/s12282-020-01210-z . .

TY  - JOUR
AU  - Prvanović, Mirjana
AU  - Nedeljković, Milica
AU  - Tanić, Nasta
AU  - Tomić, Tijana
AU  - Terzić, Tanja
AU  - Milovanović, Zorka
AU  - Maksimović, Zlatko
AU  - Tanić, Nikola
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10064
AB  - Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/mTOR protein expression may be more useful in predicting TNBC clinical course than the analysis of single protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a 'high risk' profile of TNBC.
T2  - Life (Basel, Switzerland)
T1  - Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.
VL  - 11
IS  - 11
SP  - 1247
DO  - 10.3390/life11111247
ER  - 

@article{
author = "Prvanović, Mirjana and Nedeljković, Milica and Tanić, Nasta and Tomić, Tijana and Terzić, Tanja and Milovanović, Zorka and Maksimović, Zlatko and Tanić, Nikola",
year = "2021",
abstract = "Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/mTOR protein expression may be more useful in predicting TNBC clinical course than the analysis of single protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a 'high risk' profile of TNBC.",
journal = "Life (Basel, Switzerland)",
title = "Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.",
volume = "11",
number = "11",
pages = "1247",
doi = "10.3390/life11111247"
}

Prvanović, M., Nedeljković, M., Tanić, N., Tomić, T., Terzić, T., Milovanović, Z., Maksimović, Z.,& Tanić, N.. (2021). Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.. in Life (Basel, Switzerland), 11(11), 1247.
https://doi.org/10.3390/life11111247

Prvanović M, Nedeljković M, Tanić N, Tomić T, Terzić T, Milovanović Z, Maksimović Z, Tanić N. Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.. in Life (Basel, Switzerland). 2021;11(11):1247.
doi:10.3390/life11111247 .

Prvanović, Mirjana, Nedeljković, Milica, Tanić, Nasta, Tomić, Tijana, Terzić, Tanja, Milovanović, Zorka, Maksimović, Zlatko, Tanić, Nikola, "Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer." in Life (Basel, Switzerland), 11, no. 11 (2021):1247,
https://doi.org/10.3390/life11111247 . .

TY  - JOUR
AU  - Jovanović, Mirna
AU  - Zhukovsky, Daniil
AU  - Podolski-Renić, Ana
AU  - Domračeva, Ilona
AU  - Žalubovskis, Raivis
AU  - Senćanski, Milan V.
AU  - Glišić, Sanja
AU  - Sharoyko, Vladimir
AU  - Tennikova, Tatiana
AU  - Dar'in, Dmitry
AU  - Pešić, Milica
AU  - Krasavin, Mikhail
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8532
AB  - A series of peptidomimetic compounds incorporating an electrophilic moiety was synthesized using the Ugi reaction. These compounds (termed the Ugi Michael acceptors or UMAs) were designed to target the selenocysteine catalytic residue of thioredoxin reductase 1 (TrxR1), a promising cancer target. The compounds were assessed for their potential to inhibit TrxR1 using human neuroblastoma (SH-SY5Y) cell lysate. Based on this initial screening, six compounds were selected for testing against recombinant rat TrxR1 and in the insulin assay to reveal low-micromolar to submicromolar potency of these inhibitors. The same frontrunner compounds were evaluated for their ability to exert antiproliferative activity and induce cell death and this activity was compared to the UMA effects on the levels of reactive oxygen and nitrogen species (RONS). Collectively, the UMA compounds class presented itself as a rich source of leads for TrxR1 inhibitor discovery for anticancer application. Compound 7 (DVD-445) was nominated a lead for further optimization. © 2019 Elsevier Masson SAS
T2  - European Journal of Medicinal Chemistry
T1  - Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy
VL  - 181
SP  - 111580
DO  - 10.1016/j.ejmech.2019.111580
ER  - 

@article{
author = "Jovanović, Mirna and Zhukovsky, Daniil and Podolski-Renić, Ana and Domračeva, Ilona and Žalubovskis, Raivis and Senćanski, Milan V. and Glišić, Sanja and Sharoyko, Vladimir and Tennikova, Tatiana and Dar'in, Dmitry and Pešić, Milica and Krasavin, Mikhail",
year = "2019",
abstract = "A series of peptidomimetic compounds incorporating an electrophilic moiety was synthesized using the Ugi reaction. These compounds (termed the Ugi Michael acceptors or UMAs) were designed to target the selenocysteine catalytic residue of thioredoxin reductase 1 (TrxR1), a promising cancer target. The compounds were assessed for their potential to inhibit TrxR1 using human neuroblastoma (SH-SY5Y) cell lysate. Based on this initial screening, six compounds were selected for testing against recombinant rat TrxR1 and in the insulin assay to reveal low-micromolar to submicromolar potency of these inhibitors. The same frontrunner compounds were evaluated for their ability to exert antiproliferative activity and induce cell death and this activity was compared to the UMA effects on the levels of reactive oxygen and nitrogen species (RONS). Collectively, the UMA compounds class presented itself as a rich source of leads for TrxR1 inhibitor discovery for anticancer application. Compound 7 (DVD-445) was nominated a lead for further optimization. © 2019 Elsevier Masson SAS",
journal = "European Journal of Medicinal Chemistry",
title = "Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy",
volume = "181",
pages = "111580",
doi = "10.1016/j.ejmech.2019.111580"
}

Jovanović, M., Zhukovsky, D., Podolski-Renić, A., Domračeva, I., Žalubovskis, R., Senćanski, M. V., Glišić, S., Sharoyko, V., Tennikova, T., Dar'in, D., Pešić, M.,& Krasavin, M.. (2019). Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy. in European Journal of Medicinal Chemistry, 181, 111580.
https://doi.org/10.1016/j.ejmech.2019.111580

Jovanović M, Zhukovsky D, Podolski-Renić A, Domračeva I, Žalubovskis R, Senćanski MV, Glišić S, Sharoyko V, Tennikova T, Dar'in D, Pešić M, Krasavin M. Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy. in European Journal of Medicinal Chemistry. 2019;181:111580.
doi:10.1016/j.ejmech.2019.111580 .

Jovanović, Mirna, Zhukovsky, Daniil, Podolski-Renić, Ana, Domračeva, Ilona, Žalubovskis, Raivis, Senćanski, Milan V., Glišić, Sanja, Sharoyko, Vladimir, Tennikova, Tatiana, Dar'in, Dmitry, Pešić, Milica, Krasavin, Mikhail, "Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy" in European Journal of Medicinal Chemistry, 181 (2019):111580,
https://doi.org/10.1016/j.ejmech.2019.111580 . .

TY  - JOUR
AU  - Nedeljković, Milica
AU  - Tanić, Nikola
AU  - Dramićanin, Tatjana
AU  - Milovanović, Zorka M.
AU  - Šušnjar, Snežana
AU  - Milinković, Vedrana
AU  - Vujović, Ivana
AU  - Tanić, Nasta
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7683
AB  - © 2018 Milica Nedeljković et al., published by De Gruyter Open 2018. Background: Triple negative breast cancer (TNBC) is characterized by aggressive clinical course and is unresponsive to anti-HER2 and endocrine therapy. TNBC is difficult to treat and is often lethal. Given the need to find new targets for therapy we explored clinicopathological significance of copy number gain of FGFR1 and c-MYC. Our aim was to determine the impact of FGFR1 and c-MYC copy number gain on clinical course and outcome of TNBC. Methods: FGFR1 and c-MYC gene copy number alterations were evaluated in 78 archive TNBC samples using TaqMan based quantitative real time PCR assays. Results: 50% of samples had increased c-MYC copy number. c-MYC copy number gain was associated with TNBC in contrast to ER positive cancers. Our results showed significant correlation between c-MYC copy number gain and high grade of TNBCs. This suggests that c-MYC copy number could be an useful prognostic marker for TNBC patients. c-MYC copy number gain was associated with high pTNM stage as well as lobular and medullary tumor subtypes. 43% of samples had increased FGFR1 copy number. No correlations between FGFR1 copy number gain and clinicopathological variables were observed. Conclusions: We identified c-MYC copy number gain as a prognostic marker for TNBC. Our results indicate that c- MYC may contribute to TNBC progression. We observed no significant association between c-MYC and/or FGFR1 copy number status and patient survival.
T2  - Journal of Medical Biochemistry
T1  - Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer
T1  - Značaj promena broja kopija FGFR1 i c-MYC gena u trostruko negativnim karcinomima dojke
VL  - 37
IS  - 2
SP  - 1
EP  - 8
DO  - 10.1515/jomb-2018-0012
ER  - 

@article{
author = "Nedeljković, Milica and Tanić, Nikola and Dramićanin, Tatjana and Milovanović, Zorka M. and Šušnjar, Snežana and Milinković, Vedrana and Vujović, Ivana and Tanić, Nasta",
year = "2018",
abstract = "© 2018 Milica Nedeljković et al., published by De Gruyter Open 2018. Background: Triple negative breast cancer (TNBC) is characterized by aggressive clinical course and is unresponsive to anti-HER2 and endocrine therapy. TNBC is difficult to treat and is often lethal. Given the need to find new targets for therapy we explored clinicopathological significance of copy number gain of FGFR1 and c-MYC. Our aim was to determine the impact of FGFR1 and c-MYC copy number gain on clinical course and outcome of TNBC. Methods: FGFR1 and c-MYC gene copy number alterations were evaluated in 78 archive TNBC samples using TaqMan based quantitative real time PCR assays. Results: 50% of samples had increased c-MYC copy number. c-MYC copy number gain was associated with TNBC in contrast to ER positive cancers. Our results showed significant correlation between c-MYC copy number gain and high grade of TNBCs. This suggests that c-MYC copy number could be an useful prognostic marker for TNBC patients. c-MYC copy number gain was associated with high pTNM stage as well as lobular and medullary tumor subtypes. 43% of samples had increased FGFR1 copy number. No correlations between FGFR1 copy number gain and clinicopathological variables were observed. Conclusions: We identified c-MYC copy number gain as a prognostic marker for TNBC. Our results indicate that c- MYC may contribute to TNBC progression. We observed no significant association between c-MYC and/or FGFR1 copy number status and patient survival.",
journal = "Journal of Medical Biochemistry",
title = "Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer, Značaj promena broja kopija FGFR1 i c-MYC gena u trostruko negativnim karcinomima dojke",
volume = "37",
number = "2",
pages = "1-8",
doi = "10.1515/jomb-2018-0012"
}

Nedeljković, M., Tanić, N., Dramićanin, T., Milovanović, Z. M., Šušnjar, S., Milinković, V., Vujović, I.,& Tanić, N.. (2018). Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer. in Journal of Medical Biochemistry, 37(2), 1-8.
https://doi.org/10.1515/jomb-2018-0012

Nedeljković M, Tanić N, Dramićanin T, Milovanović ZM, Šušnjar S, Milinković V, Vujović I, Tanić N. Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer. in Journal of Medical Biochemistry. 2018;37(2):1-8.
doi:10.1515/jomb-2018-0012 .

Nedeljković, Milica, Tanić, Nikola, Dramićanin, Tatjana, Milovanović, Zorka M., Šušnjar, Snežana, Milinković, Vedrana, Vujović, Ivana, Tanić, Nasta, "Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer" in Journal of Medical Biochemistry, 37, no. 2 (2018):1-8,
https://doi.org/10.1515/jomb-2018-0012 . .

TY  - JOUR
AU  - Pešić, Milica
AU  - Podolski-Renić, Ana
AU  - Stojković, Sonja
AU  - Matović, Branko
AU  - Zmejkoski, Danica
AU  - Kojić, Vesna
AU  - Bogdanović, Gordana
AU  - Pavicevic, Aleksandra
AU  - Mojovic, Milos
AU  - Savić, Aleksandar
AU  - Milenković, Ivana
AU  - Kalauzi, Aleksandar
AU  - Radotić, Ksenija
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/519
AB  - Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
T2  - Chemico-Biological Interactions
T1  - Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity
VL  - 232
SP  - 85
EP  - 93
DO  - 10.1016/j.cbi.2015.03.013
ER  - 

@article{
author = "Pešić, Milica and Podolski-Renić, Ana and Stojković, Sonja and Matović, Branko and Zmejkoski, Danica and Kojić, Vesna and Bogdanović, Gordana and Pavicevic, Aleksandra and Mojovic, Milos and Savić, Aleksandar and Milenković, Ivana and Kalauzi, Aleksandar and Radotić, Ksenija",
year = "2015",
abstract = "Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine. (C) 2015 Elsevier Ireland Ltd. All rights reserved.",
journal = "Chemico-Biological Interactions",
title = "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity",
volume = "232",
pages = "85-93",
doi = "10.1016/j.cbi.2015.03.013"
}

Pešić, M., Podolski-Renić, A., Stojković, S., Matović, B., Zmejkoski, D., Kojić, V., Bogdanović, G., Pavicevic, A., Mojovic, M., Savić, A., Milenković, I., Kalauzi, A.,& Radotić, K.. (2015). Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions, 232, 85-93.
https://doi.org/10.1016/j.cbi.2015.03.013

Pešić M, Podolski-Renić A, Stojković S, Matović B, Zmejkoski D, Kojić V, Bogdanović G, Pavicevic A, Mojovic M, Savić A, Milenković I, Kalauzi A, Radotić K. Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions. 2015;232:85-93.
doi:10.1016/j.cbi.2015.03.013 .

Pešić, Milica, Podolski-Renić, Ana, Stojković, Sonja, Matović, Branko, Zmejkoski, Danica, Kojić, Vesna, Bogdanović, Gordana, Pavicevic, Aleksandra, Mojovic, Milos, Savić, Aleksandar, Milenković, Ivana, Kalauzi, Aleksandar, Radotić, Ksenija, "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity" in Chemico-Biological Interactions, 232 (2015):85-93,
https://doi.org/10.1016/j.cbi.2015.03.013 . .

TY  - JOUR
AU  - Stanković, Tijana
AU  - Milinković, Vedrana
AU  - Banković, Jasna Z.
AU  - Dinić, Jelena
AU  - Tanić, Nasta
AU  - Dramićanin, Tatjana
AU  - Tanić, Nikola
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/143
AB  - p53, p16 and PTEN are the most commonly altered tumor suppressor genes in human cancers. In the present study, we compared the presence of individual and multiple alterations of these tumor suppressors in non-small cell lung carcinoma (NSCLC), glioma and breast carcinoma, in order to evaluate specificity of each tumor type regarding the number of altered genes, as well as their combinations. We tested the mutational status, loss of heterozygosity and methylation status of these genes. Effects of gene alterations on patients survival were also assessed. In NSCLC samples, single gene alterations occurred rarely, while there was considerable increase in incidence of double gene alterations. Furthermore, coexistence of aberrant p53, PTEN and p16 was the most frequent and had significant adverse effect on the survival of NSCLC patients. On the contrary, in glioma and breast cancer specimens, substantial number of cases had aberrant single gene only. Moreover, glioma and breast carcinoma also differ in genotypes that were predominant. Specifically, in glioma samples, prevalent were co-alterations of PTEN and p16, followed by aberrant only PTEN. In breast cancer samples, alterations in all three genes as well as in p53 and p16 were the most common. Moreover, PTEN was altered exclusively with aberrant p53, with statistically significant correlation among them. Overall, our results suggest that NSCLC, glioma and breast cancer need different approaches in molecular diagnosis and treatment with particular attention toward the number and combination of targeted genes. (C) 2014 Elsevier Masson SAS. All rights reserved.
T2  - Biomedicine and Pharmacotherapy
T1  - Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples
VL  - 68
IS  - 5
SP  - 521
EP  - 526
DO  - 10.1016/j.biopha.2014.03.014
ER  - 

@article{
author = "Stanković, Tijana and Milinković, Vedrana and Banković, Jasna Z. and Dinić, Jelena and Tanić, Nasta and Dramićanin, Tatjana and Tanić, Nikola",
year = "2014",
abstract = "p53, p16 and PTEN are the most commonly altered tumor suppressor genes in human cancers. In the present study, we compared the presence of individual and multiple alterations of these tumor suppressors in non-small cell lung carcinoma (NSCLC), glioma and breast carcinoma, in order to evaluate specificity of each tumor type regarding the number of altered genes, as well as their combinations. We tested the mutational status, loss of heterozygosity and methylation status of these genes. Effects of gene alterations on patients survival were also assessed. In NSCLC samples, single gene alterations occurred rarely, while there was considerable increase in incidence of double gene alterations. Furthermore, coexistence of aberrant p53, PTEN and p16 was the most frequent and had significant adverse effect on the survival of NSCLC patients. On the contrary, in glioma and breast cancer specimens, substantial number of cases had aberrant single gene only. Moreover, glioma and breast carcinoma also differ in genotypes that were predominant. Specifically, in glioma samples, prevalent were co-alterations of PTEN and p16, followed by aberrant only PTEN. In breast cancer samples, alterations in all three genes as well as in p53 and p16 were the most common. Moreover, PTEN was altered exclusively with aberrant p53, with statistically significant correlation among them. Overall, our results suggest that NSCLC, glioma and breast cancer need different approaches in molecular diagnosis and treatment with particular attention toward the number and combination of targeted genes. (C) 2014 Elsevier Masson SAS. All rights reserved.",
journal = "Biomedicine and Pharmacotherapy",
title = "Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples",
volume = "68",
number = "5",
pages = "521-526",
doi = "10.1016/j.biopha.2014.03.014"
}

Stanković, T., Milinković, V., Banković, J. Z., Dinić, J., Tanić, N., Dramićanin, T.,& Tanić, N.. (2014). Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples. in Biomedicine and Pharmacotherapy, 68(5), 521-526.
https://doi.org/10.1016/j.biopha.2014.03.014

Stanković T, Milinković V, Banković JZ, Dinić J, Tanić N, Dramićanin T, Tanić N. Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples. in Biomedicine and Pharmacotherapy. 2014;68(5):521-526.
doi:10.1016/j.biopha.2014.03.014 .

Stanković, Tijana, Milinković, Vedrana, Banković, Jasna Z., Dinić, Jelena, Tanić, Nasta, Dramićanin, Tatjana, Tanić, Nikola, "Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples" in Biomedicine and Pharmacotherapy, 68, no. 5 (2014):521-526,
https://doi.org/10.1016/j.biopha.2014.03.014 . .

TY  - JOUR
AU  - Tanić, Nasta
AU  - Milinković, Vedrana
AU  - Dramićanin, Tatjana
AU  - Nedeljković, Milica
AU  - Stanković, Tijana
AU  - Milovanović, Zorka M.
AU  - Šušnjar, Snežana
AU  - Milošević, Verica
AU  - Šošić-Jurjević, Branka
AU  - Džodić, Radan R.
AU  - Tanić, Nikola
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5745
AB  - Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGFR), cyclinD1 (CCND1) and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential PCR. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patients outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients.
T2  - Journal of Medical Biochemistry
T1  - Amplification of Cycline D1, C-Myc and Egfr Oncogenes in Tumour Samples of Breast Cancer Patients
VL  - 32
IS  - 4
DO  - 10.2478/jomb-2014-0005
ER  - 

@article{
author = "Tanić, Nasta and Milinković, Vedrana and Dramićanin, Tatjana and Nedeljković, Milica and Stanković, Tijana and Milovanović, Zorka M. and Šušnjar, Snežana and Milošević, Verica and Šošić-Jurjević, Branka and Džodić, Radan R. and Tanić, Nikola",
year = "2013",
abstract = "Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGFR), cyclinD1 (CCND1) and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential PCR. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patients outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients.",
journal = "Journal of Medical Biochemistry",
title = "Amplification of Cycline D1, C-Myc and Egfr Oncogenes in Tumour Samples of Breast Cancer Patients",
volume = "32",
number = "4",
doi = "10.2478/jomb-2014-0005"
}

Tanić, N., Milinković, V., Dramićanin, T., Nedeljković, M., Stanković, T., Milovanović, Z. M., Šušnjar, S., Milošević, V., Šošić-Jurjević, B., Džodić, R. R.,& Tanić, N.. (2013). Amplification of Cycline D1, C-Myc and Egfr Oncogenes in Tumour Samples of Breast Cancer Patients. in Journal of Medical Biochemistry, 32(4).
https://doi.org/10.2478/jomb-2014-0005

Tanić N, Milinković V, Dramićanin T, Nedeljković M, Stanković T, Milovanović ZM, Šušnjar S, Milošević V, Šošić-Jurjević B, Džodić RR, Tanić N. Amplification of Cycline D1, C-Myc and Egfr Oncogenes in Tumour Samples of Breast Cancer Patients. in Journal of Medical Biochemistry. 2013;32(4).
doi:10.2478/jomb-2014-0005 .

Tanić, Nasta, Milinković, Vedrana, Dramićanin, Tatjana, Nedeljković, Milica, Stanković, Tijana, Milovanović, Zorka M., Šušnjar, Snežana, Milošević, Verica, Šošić-Jurjević, Branka, Džodić, Radan R., Tanić, Nikola, "Amplification of Cycline D1, C-Myc and Egfr Oncogenes in Tumour Samples of Breast Cancer Patients" in Journal of Medical Biochemistry, 32, no. 4 (2013),
https://doi.org/10.2478/jomb-2014-0005 . .

TY  - JOUR
AU  - Tanić, Nasta
AU  - Milašin, Jelena
AU  - Dramićanin, Tatjana
AU  - Bošković, Maja
AU  - Vukadinovic, Miroslav
AU  - Milošević, Verica
AU  - Tanić, Nikola
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5747
AB  - Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. There fore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycD1 in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycD1 and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours.
T2  - Journal of Medical Biochemistry
T1  - TP53 AND C-MYC CO-ALTERATIONS - A HALLMARK OF ORAL CANCER PROGRESSION
VL  - 32
IS  - 4
SP  - 380
EP  - 388
DO  - 10.2478/jomb-2014-0009
ER  - 

@article{
author = "Tanić, Nasta and Milašin, Jelena and Dramićanin, Tatjana and Bošković, Maja and Vukadinovic, Miroslav and Milošević, Verica and Tanić, Nikola",
year = "2013",
abstract = "Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. There fore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycD1 in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycD1 and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours.",
journal = "Journal of Medical Biochemistry",
title = "TP53 AND C-MYC CO-ALTERATIONS - A HALLMARK OF ORAL CANCER PROGRESSION",
volume = "32",
number = "4",
pages = "380-388",
doi = "10.2478/jomb-2014-0009"
}

Tanić, N., Milašin, J., Dramićanin, T., Bošković, M., Vukadinovic, M., Milošević, V.,& Tanić, N.. (2013). TP53 AND C-MYC CO-ALTERATIONS - A HALLMARK OF ORAL CANCER PROGRESSION. in Journal of Medical Biochemistry, 32(4), 380-388.
https://doi.org/10.2478/jomb-2014-0009

Tanić N, Milašin J, Dramićanin T, Bošković M, Vukadinovic M, Milošević V, Tanić N. TP53 AND C-MYC CO-ALTERATIONS - A HALLMARK OF ORAL CANCER PROGRESSION. in Journal of Medical Biochemistry. 2013;32(4):380-388.
doi:10.2478/jomb-2014-0009 .

Tanić, Nasta, Milašin, Jelena, Dramićanin, Tatjana, Bošković, Maja, Vukadinovic, Miroslav, Milošević, Verica, Tanić, Nikola, "TP53 AND C-MYC CO-ALTERATIONS - A HALLMARK OF ORAL CANCER PROGRESSION" in Journal of Medical Biochemistry, 32, no. 4 (2013):380-388,
https://doi.org/10.2478/jomb-2014-0009 . .

TY  - JOUR
AU  - Tanić, Nikola
AU  - Milovanović, Zorka M.
AU  - Tanić, Nasta
AU  - Džodić, Radan R.
AU  - Juranic, Zorica
AU  - Šušnjar, Snežana
AU  - Plesinac-Karapandzic, Vesna
AU  - Tatic, Svetislav
AU  - Dramićanin, Tatjana
AU  - Davidović, Radoslav S.
AU  - Dimitrijević, Bogomir B.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5073
AB  - Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.
T2  - Cancer Biology and Therapy
T1  - The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients
VL  - 13
IS  - 12
SP  - 1165
EP  - 1174
DO  - 10.4161/cbt.21346
ER  - 

@article{
author = "Tanić, Nikola and Milovanović, Zorka M. and Tanić, Nasta and Džodić, Radan R. and Juranic, Zorica and Šušnjar, Snežana and Plesinac-Karapandzic, Vesna and Tatic, Svetislav and Dramićanin, Tatjana and Davidović, Radoslav S. and Dimitrijević, Bogomir B.",
year = "2012",
abstract = "Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.",
journal = "Cancer Biology and Therapy",
title = "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients",
volume = "13",
number = "12",
pages = "1165-1174",
doi = "10.4161/cbt.21346"
}

Tanić, N., Milovanović, Z. M., Tanić, N., Džodić, R. R., Juranic, Z., Šušnjar, S., Plesinac-Karapandzic, V., Tatic, S., Dramićanin, T., Davidović, R. S.,& Dimitrijević, B. B.. (2012). The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology and Therapy, 13(12), 1165-1174.
https://doi.org/10.4161/cbt.21346

Tanić N, Milovanović ZM, Tanić N, Džodić RR, Juranic Z, Šušnjar S, Plesinac-Karapandzic V, Tatic S, Dramićanin T, Davidović RS, Dimitrijević BB. The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology and Therapy. 2012;13(12):1165-1174.
doi:10.4161/cbt.21346 .

Tanić, Nikola, Milovanović, Zorka M., Tanić, Nasta, Džodić, Radan R., Juranic, Zorica, Šušnjar, Snežana, Plesinac-Karapandzic, Vesna, Tatic, Svetislav, Dramićanin, Tatjana, Davidović, Radoslav S., Dimitrijević, Bogomir B., "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients" in Cancer Biology and Therapy, 13, no. 12 (2012):1165-1174,
https://doi.org/10.4161/cbt.21346 . .