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://www.mdpi.com/2075-1729/11/11/1247
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8621563
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4698
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.
PB  - Basel: MDPI
T2  - Life (Basel, Switzerland)
T1  - Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.
IS  - 11
VL  - 11
DO  - 10.3390/life11111247
SP  - 1247
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.",
publisher = "Basel: MDPI",
journal = "Life (Basel, Switzerland)",
title = "Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.",
number = "11",
volume = "11",
doi = "10.3390/life11111247",
pages = "1247"
}

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)
Basel: MDPI., 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  - Nedeljković, Milica
AU  - Tanić, Nasta
AU  - Prvanović, Mirjana
AU  - Milovanović, Zorka
AU  - Tanić, Nikola
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4233
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.
PB  - Springer Japan
T2  - Breast Cancer
T1  - Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer
IS  - 3
VL  - 28
DO  - 10.1007/s12282-020-01210-z
SP  - 727
EP  - 736
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.",
publisher = "Springer Japan",
journal = "Breast Cancer",
title = "Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer",
number = "3",
volume = "28",
doi = "10.1007/s12282-020-01210-z",
pages = "727-736"
}

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
Springer Japan., 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  - Nedeljković, Milica
AU  - Tanić, Nikola
AU  - Dramićanin, Tatjana
AU  - Milovanović, Zorka
AU  - Šušnjar, Snežana
AU  - Milinković, Vedrana
AU  - Vujović, Ivana
AU  - Tanić, Nasta
PY  - 2018
UR  - http://content.sciendo.com/view/journals/jomb/ahead-of-print/article-10.1515-jomb-2018-0012.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3062
AB  - 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
DO  - 10.1515/jomb-2018-0012
ER  - 

@article{
author = "Nedeljković, Milica and Tanić, Nikola and Dramićanin, Tatjana and Milovanović, Zorka and Šušnjar, Snežana and Milinković, Vedrana and Vujović, Ivana and Tanić, Nasta",
year = "2018",
abstract = "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",
doi = "10.1515/jomb-2018-0012"
}

Nedeljković, M., Tanić, N., Dramićanin, T., Milovanović, Z., 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.
https://doi.org/10.1515/jomb-2018-0012

Nedeljković M, Tanić N, Dramićanin T, Milovanović Z, 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;.
doi:10.1515/jomb-2018-0012 .

Nedeljković, Milica, Tanić, Nikola, Dramićanin, Tatjana, Milovanović, Zorka, 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 (2018),
https://doi.org/10.1515/jomb-2018-0012 . .