TY  - CONF
AU  - Nedeljković, Milica
AU  - Dramićanin, Tatjana
AU  - Prvanović, Mirjana
AU  - Murganić, Blagoje
AU  - Tomić, Tijana
AU  - Ademović, Nejla
AU  - Milovanović, Zorka
AU  - Tanić, Nikola
AU  - Tanić, Nasta
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6692
AB  - Background: Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. Multiple interconnected factors determine BC response to therapy and clinical outcome. TP53 and PTEN are the most frequently altered tumor suppressor genes (TSGs) in human cancers. Material and methods: To determine the potential influence of TSGs on the response to therapy we analyzed alterations of TP53 and PTEN in 90 BC specimens. The specimens were stratified based on systemic adjuvant therapy (hormonal therapy only (HT), HT and chemotherapy (HT/CHT), HT/CHT and biological therapy (HT/CHT/H). Functional inactivation of TP53 by mutations and/or loss of heterozygosity (LOH) and PTEN by LOH and/or promoter hypermethylation, were tested using single-strand conformational polymorphism (SSCP) analysis, gene sequencing, fragment analysis and methylation-specific PCR (MS-PCR) methods respectively. Results: Altered TP53 was found in 63/90 specimens (70%) while 54/90 (60%) had inactivated PTEN. Inactivation of PTEN was more frequent in tumors with altered TP53. Patients with altered TP53, lived shorter (p=0.0007) compared to those with wild type (wt) gene. The survival of patients with both TSGs altered was shorter compared to wt genes (p=0.024). Patients with wtTP53 treated with HT had longer survival (p=0.000001) when compared to all other groups. Women with both TSGs altered who received tamoxifen lived shorter than those on HT with both/one TSGs intact (p = 0.03). Conclusion: Patients with wtTP53 showed significantly better therapy response regardless of type of therapy, compared to carriers of altered TP53.
PB  - Beograd : Srpsko društvo istraživača raka
C3  - Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event
T1  - Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6692
ER  - 

@conference{
author = "Nedeljković, Milica and Dramićanin, Tatjana and Prvanović, Mirjana and Murganić, Blagoje and Tomić, Tijana and Ademović, Nejla and Milovanović, Zorka and Tanić, Nikola and Tanić, Nasta",
year = "2021",
abstract = "Background: Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. Multiple interconnected factors determine BC response to therapy and clinical outcome. TP53 and PTEN are the most frequently altered tumor suppressor genes (TSGs) in human cancers. Material and methods: To determine the potential influence of TSGs on the response to therapy we analyzed alterations of TP53 and PTEN in 90 BC specimens. The specimens were stratified based on systemic adjuvant therapy (hormonal therapy only (HT), HT and chemotherapy (HT/CHT), HT/CHT and biological therapy (HT/CHT/H). Functional inactivation of TP53 by mutations and/or loss of heterozygosity (LOH) and PTEN by LOH and/or promoter hypermethylation, were tested using single-strand conformational polymorphism (SSCP) analysis, gene sequencing, fragment analysis and methylation-specific PCR (MS-PCR) methods respectively. Results: Altered TP53 was found in 63/90 specimens (70%) while 54/90 (60%) had inactivated PTEN. Inactivation of PTEN was more frequent in tumors with altered TP53. Patients with altered TP53, lived shorter (p=0.0007) compared to those with wild type (wt) gene. The survival of patients with both TSGs altered was shorter compared to wt genes (p=0.024). Patients with wtTP53 treated with HT had longer survival (p=0.000001) when compared to all other groups. Women with both TSGs altered who received tamoxifen lived shorter than those on HT with both/one TSGs intact (p = 0.03). Conclusion: Patients with wtTP53 showed significantly better therapy response regardless of type of therapy, compared to carriers of altered TP53.",
publisher = "Beograd : Srpsko društvo istraživača raka",
journal = "Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event",
title = "Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6692"
}

Nedeljković, M., Dramićanin, T., Prvanović, M., Murganić, B., Tomić, T., Ademović, N., Milovanović, Z., Tanić, N.,& Tanić, N.. (2021). Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy. in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event
Beograd : Srpsko društvo istraživača raka., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6692

Nedeljković M, Dramićanin T, Prvanović M, Murganić B, Tomić T, Ademović N, Milovanović Z, Tanić N, Tanić N. Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy. in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event. 2021;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6692 .

Nedeljković, Milica, Dramićanin, Tatjana, Prvanović, Mirjana, Murganić, Blagoje, Tomić, Tijana, Ademović, Nejla, Milovanović, Zorka, Tanić, Nikola, Tanić, Nasta, "Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy" in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event (2021):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6692 .

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 . .