TY  - JOUR
AU  - Bovan, Dijana
AU  - Krajnović, Tamara
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mijatović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6576
AB  - Background: Shikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6. 
Methods and results: All examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann‐like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death—anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. 
Conclusions: Herein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.
PB  - Springer Nature
T2  - Molecular Biology Reports
T1  - Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro
IS  - 1
VL  - 51
DO  - 10.1007/s11033-023-09093-x
SP  - 218
ER  - 

@article{
author = "Bovan, Dijana and Krajnović, Tamara and Vuković, Nenad L. and Vukić, Milena D. and Mijatović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2024",
abstract = "Background: Shikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6. 
Methods and results: All examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann‐like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death—anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. 
Conclusions: Herein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.",
publisher = "Springer Nature",
journal = "Molecular Biology Reports",
title = "Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro",
number = "1",
volume = "51",
doi = "10.1007/s11033-023-09093-x",
pages = "218"
}

Bovan, D., Krajnović, T., Vuković, N. L., Vukić, M. D., Mijatović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2024). Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro. in Molecular Biology Reports
Springer Nature., 51(1), 218.
https://doi.org/10.1007/s11033-023-09093-x

Bovan D, Krajnović T, Vuković NL, Vukić MD, Mijatović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro. in Molecular Biology Reports. 2024;51(1):218.
doi:10.1007/s11033-023-09093-x .

Bovan, Dijana, Krajnović, Tamara, Vuković, Nenad L., Vukić, Milena D., Mijatović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro" in Molecular Biology Reports, 51, no. 1 (2024):218,
https://doi.org/10.1007/s11033-023-09093-x . .

TY  - CONF
AU  - Medić-Milijić, Nataša
AU  - Jovanić, Irena
AU  - Nedeljković, Milica
AU  - Spurnić, Igor
AU  - Milovanović, Zorka
AU  - Ademović, Nejla
AU  - Tanić, Nikola
AU  - Tanić, Nasta
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6409
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 breast cancer 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 role PD-L1 (Programmed Death-Ligand 1), EGFR
(Epidermal Growth Factor Receptor) and Androgen Receptor (AR) expression in
TNBC promotion, progression and response to therapy,
This is a retrospective analysis of 125 patients with triple-negative breast cancer
operated at the Institute of Oncology and Radiology of Serbia in the period
2009 to 2014. The expression of PD-L1, EGFR and AR wеre observed using the
immunohistochemical staining method. PD-L1 expression was determined using
the combined positive score (CPS), EGFR expression was determined using the
Allred scoring system with cut-off values: ≤4 and >4 (low/high expression) while
determining the expression status of AR involved a quantitative method based on
the percentage of nuclear expression of malignant cells of any intensity (cut-off value
for positive expression was ≥10%).
Elevated expression of PD-L1 significantly correlated with higher tumor grade
(p=0.0002), nuclear grade (p=0.0007) and loco-regional recurrence (p=0.0146).
Alone, it did not show any significant influence on survival (DFI or OS). Contrary
to this, the expression of AR showed an impact on DFI (Disease Free Interval,
p=0.0171). In addition, elevated AR expression significantly correlated with higher
tumor grade. Interestingly, the expression of PD-L1 and AR significantly correlated
(Spearman r -0.2747; 95% confidence interval -0.4339 to -0.09895: P (two-tailed)
0.0019) and we were able to make two groups of patients, those who had high simultaneous expression of both genes and those who had low expression. Our
results revealed that simultaneous high expression of PD-L1 and AR significantly
correlates with tumor grade (p=0.05), nuclear grade (p=o.0242) and metastases
(p=0.0497) and has significant impact on DFI (p=0.0191) and OS (overall survival)
(p=0.0471). Notably, the expression of Ki67 absolutely correlates with the expression
of PD-L1 and AR, has the same pattern of expression. Moreover, reduced expression
of EGFR contributes to metastases (p=0.0249) and worse OS (p=0.0127).
In conclusion, we believe that concurrent examination of PD-L1, AR, EGFR and
Ki67 protein expression may be more useful in predicting TNBC clinical course
than the analysis of single protein expression. Specifically, our results showed
that simultaneous high expression of PD-L1 and AR, followed by Ki67 expression
constitutes a ‘high risk’ profile of TNBC. Combining these results with our previous
findings on PTEN-reduced/PI3K-high/mTOR-high expression could be the
promising formula.
AB  - Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од карцинома
код жена. Троструко негативни карцином дојке (ТНБЦ) је најагресивнији
његов подтип који се одликује високом стопом рецидива, учесталом појавом
удаљених метастаза, као и лошим утицајем на укупно преживљавање. Циљ
ове студије је био одређивање експресије PD-L1 (Programmed Death-Ligand
1), EGFR (Epidermal Growth Factor Receptor) и андроген рецептора (АР) код
пацијенткиња оболелих од ТНКД као и да се утврди да ли њихова измењена
експресија корелира са клиничким током болести, прогресијом болести и/или
одговором на примењену терапију.
Овом ретроспективном студијом обухваћено је 125 пацијенткиња оболелох
од троструко негативних карцинома дојке које су у периоду 2009. до 2014.
године оперисане у Институту за онкологију и радиологију Србије. Експресија
PD-L1, EGFR и AR је одређена имунохистохемијском методом бојења. Статус
експресије PD-L1 је одређен коришћењем комбинованог позитивног скора
(ЦПС), експресија EGFR је одређена коришћењем Allred scoring система са
граничним вредностима: ≤4 и >4 (ниска/висока експресија), док је одређивање
статуса експресије AR подразумевало квантитативну методу базирану на
проценту нуклеарне експресије малигних ћелија било ког интезитета (гранична
вредност за позитивну експресију била је ≥10%).
Ова студија је показала да је повећана експресија PD-L1 у значајној
корелерацији са вишим хистолошким градусом тумора (p=0,0002), нуклеарним градусом (p=0,0007) и са чешћом појавом локо-регионалних рецидива
(p=0,0146). Повећана експресија PD-L1 протеина нема значањијег утицаја на
дужину интервала без болести и на укупно преживљавање (DFI и ОS). Супротно
овоме, експресија АR је у асоцијацији са DFI (p=0,0171), и у корелацији је са
вишим градусом тумора. Утврђено је такође да постоји значајна повезаност у
симултаној експресији ова два протеина , PD-L1 и АR (Spearman р -0,2747; 95%
интервал поверења -0,4339 до -0,09895: P (двострано) 0,0019). Истовремено
јасно су дефинисане две групе пацијенткиња-са повишеном експресијом PD-L1
и АR и са смањеном експресијом ова два протеина и утврђено је да симултана
експресија корелира са градусом тумора (п=0,05), нуклеарним градусом
(p=0.0242) и учесталошћу појаве метастаза (p=0,0497). Истовремено, симултана
експресија утиче на DFI (p=0,0191) и OS (p=0,0471). Запажено је да експресија
Ki67 значајно корелира са експресијом PD-L1 и AR, као и да има исти образац
експресије, док смањена експресија EGFR доприноси чешћој појави метастаза
(p=0,0249) и краћем интервалу укупног преживљавања (p=0,0127).
Добијени резултати сугеришу да би истовремено испитивање експресије
протеина PD-L1, АR, ЕGFR и Ki67 могло бити корисније у предвиђању
клиничког тока ТНКД од појединачних анализа. Наши резултати су показали
да би група ТНКД ”високог ризика“ могла бити она са симултаном високом
експресијом PD-L1 и АR, праћена високом експресијом Ki67.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients
T1  - Прогностички и клинички значај експресије PD-L1, EGFR и андрогеног рецептора (АР) код пацијената са троструко негативним карциномом дојке (ТНКД)
SP  - 67
EP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6409
ER  - 

@conference{
author = "Medić-Milijić, Nataša and Jovanić, Irena and Nedeljković, Milica and Spurnić, Igor and Milovanović, Zorka and Ademović, Nejla and Tanić, Nikola and Tanić, Nasta",
year = "2023",
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 breast cancer 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 role PD-L1 (Programmed Death-Ligand 1), EGFR
(Epidermal Growth Factor Receptor) and Androgen Receptor (AR) expression in
TNBC promotion, progression and response to therapy,
This is a retrospective analysis of 125 patients with triple-negative breast cancer
operated at the Institute of Oncology and Radiology of Serbia in the period
2009 to 2014. The expression of PD-L1, EGFR and AR wеre observed using the
immunohistochemical staining method. PD-L1 expression was determined using
the combined positive score (CPS), EGFR expression was determined using the
Allred scoring system with cut-off values: ≤4 and >4 (low/high expression) while
determining the expression status of AR involved a quantitative method based on
the percentage of nuclear expression of malignant cells of any intensity (cut-off value
for positive expression was ≥10%).
Elevated expression of PD-L1 significantly correlated with higher tumor grade
(p=0.0002), nuclear grade (p=0.0007) and loco-regional recurrence (p=0.0146).
Alone, it did not show any significant influence on survival (DFI or OS). Contrary
to this, the expression of AR showed an impact on DFI (Disease Free Interval,
p=0.0171). In addition, elevated AR expression significantly correlated with higher
tumor grade. Interestingly, the expression of PD-L1 and AR significantly correlated
(Spearman r -0.2747; 95% confidence interval -0.4339 to -0.09895: P (two-tailed)
0.0019) and we were able to make two groups of patients, those who had high simultaneous expression of both genes and those who had low expression. Our
results revealed that simultaneous high expression of PD-L1 and AR significantly
correlates with tumor grade (p=0.05), nuclear grade (p=o.0242) and metastases
(p=0.0497) and has significant impact on DFI (p=0.0191) and OS (overall survival)
(p=0.0471). Notably, the expression of Ki67 absolutely correlates with the expression
of PD-L1 and AR, has the same pattern of expression. Moreover, reduced expression
of EGFR contributes to metastases (p=0.0249) and worse OS (p=0.0127).
In conclusion, we believe that concurrent examination of PD-L1, AR, EGFR and
Ki67 protein expression may be more useful in predicting TNBC clinical course
than the analysis of single protein expression. Specifically, our results showed
that simultaneous high expression of PD-L1 and AR, followed by Ki67 expression
constitutes a ‘high risk’ profile of TNBC. Combining these results with our previous
findings on PTEN-reduced/PI3K-high/mTOR-high expression could be the
promising formula., Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од карцинома
код жена. Троструко негативни карцином дојке (ТНБЦ) је најагресивнији
његов подтип који се одликује високом стопом рецидива, учесталом појавом
удаљених метастаза, као и лошим утицајем на укупно преживљавање. Циљ
ове студије је био одређивање експресије PD-L1 (Programmed Death-Ligand
1), EGFR (Epidermal Growth Factor Receptor) и андроген рецептора (АР) код
пацијенткиња оболелих од ТНКД као и да се утврди да ли њихова измењена
експресија корелира са клиничким током болести, прогресијом болести и/или
одговором на примењену терапију.
Овом ретроспективном студијом обухваћено је 125 пацијенткиња оболелох
од троструко негативних карцинома дојке које су у периоду 2009. до 2014.
године оперисане у Институту за онкологију и радиологију Србије. Експресија
PD-L1, EGFR и AR је одређена имунохистохемијском методом бојења. Статус
експресије PD-L1 је одређен коришћењем комбинованог позитивног скора
(ЦПС), експресија EGFR је одређена коришћењем Allred scoring система са
граничним вредностима: ≤4 и >4 (ниска/висока експресија), док је одређивање
статуса експресије AR подразумевало квантитативну методу базирану на
проценту нуклеарне експресије малигних ћелија било ког интезитета (гранична
вредност за позитивну експресију била је ≥10%).
Ова студија је показала да је повећана експресија PD-L1 у значајној
корелерацији са вишим хистолошким градусом тумора (p=0,0002), нуклеарним градусом (p=0,0007) и са чешћом појавом локо-регионалних рецидива
(p=0,0146). Повећана експресија PD-L1 протеина нема значањијег утицаја на
дужину интервала без болести и на укупно преживљавање (DFI и ОS). Супротно
овоме, експресија АR је у асоцијацији са DFI (p=0,0171), и у корелацији је са
вишим градусом тумора. Утврђено је такође да постоји значајна повезаност у
симултаној експресији ова два протеина , PD-L1 и АR (Spearman р -0,2747; 95%
интервал поверења -0,4339 до -0,09895: P (двострано) 0,0019). Истовремено
јасно су дефинисане две групе пацијенткиња-са повишеном експресијом PD-L1
и АR и са смањеном експресијом ова два протеина и утврђено је да симултана
експресија корелира са градусом тумора (п=0,05), нуклеарним градусом
(p=0.0242) и учесталошћу појаве метастаза (p=0,0497). Истовремено, симултана
експресија утиче на DFI (p=0,0191) и OS (p=0,0471). Запажено је да експресија
Ki67 значајно корелира са експресијом PD-L1 и AR, као и да има исти образац
експресије, док смањена експресија EGFR доприноси чешћој појави метастаза
(p=0,0249) и краћем интервалу укупног преживљавања (p=0,0127).
Добијени резултати сугеришу да би истовремено испитивање експресије
протеина PD-L1, АR, ЕGFR и Ki67 могло бити корисније у предвиђању
клиничког тока ТНКД од појединачних анализа. Наши резултати су показали
да би група ТНКД ”високог ризика“ могла бити она са симултаном високом
експресијом PD-L1 и АR, праћена високом експресијом Ki67.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients, Прогностички и клинички значај експресије PD-L1, EGFR и андрогеног рецептора (АР) код пацијената са троструко негативним карциномом дојке (ТНКД)",
pages = "67-70",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6409"
}

Medić-Milijić, N., Jovanić, I., Nedeljković, M., Spurnić, I., Milovanović, Z., Ademović, N., Tanić, N.,& Tanić, N.. (2023). Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 67-70.
https://hdl.handle.net/21.15107/rcub_ibiss_6409

Medić-Milijić N, Jovanić I, Nedeljković M, Spurnić I, Milovanović Z, Ademović N, Tanić N, Tanić N. Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:67-70.
https://hdl.handle.net/21.15107/rcub_ibiss_6409 .

Medić-Milijić, Nataša, Jovanić, Irena, Nedeljković, Milica, Spurnić, Igor, Milovanović, Zorka, Ademović, Nejla, Tanić, Nikola, Tanić, Nasta, "Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):67-70,
https://hdl.handle.net/21.15107/rcub_ibiss_6409 .

TY  - CONF
AU  - Tanić, Nikola
AU  - Blagojević, Danijela
AU  - Milanović, Ivana
AU  - Imširović, Mirela
AU  - Lazić, Sandra
AU  - Maksimović, Zlatko
AU  - Tanić, Nasta
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6328
AB  - Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused COVID-19 pandemic. This coronavirus disease pandemic demonstrated the importance of diagnostic testing in disease outbreak monitoring and control. So, reliable and accurate testing for SARS-CoV-2 was the principal prerequisite for preventing the spread of COVID-19.
Methods: Real Time RT-PCR (RT-qPCR) unquestionably represent the most reliable, rapid and sensitive method for detection of SARS-CoV-2 RNA. However, there are numerous different assays, protocols, reagents, instruments and result analysis methods in use without certified standards, standardized RNA extraction and reporting procedures. Therefore, in practice, the reliability of RT-qPCR results depends on a number of parameters that include sample collection and processing, method of RNA extraction, choice of assay, efficiency of assay, choice of instrument, analysis method as well as operator intervention.
Results: Here we present comparative analyses of the efficiency and sensitivity of 10 different amplification assays, as well as the relevance of manual RNA extractions compared to automatic one. Our results revealed that manual viral RNA extraction should be a method of choice for high sensitivity. In addition, amplification assays targeting three SARS-CoV-2 genes are much more efficient from those targeting one.
Conclusion: Unfortunately, RT-qPCR is almost exclusively used as qualitative diagnostic test for SARSCoV-2. We think that the ideal testing regimen would involve not just qualitative detection of SARS-CoV-2 but reliable and meaningful quantitative reporting of viral load.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Diagnostic testing for SARS-COV-2 by Real-time RT-PCR
IS  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6328
ER  - 

@conference{
author = "Tanić, Nikola and Blagojević, Danijela and Milanović, Ivana and Imširović, Mirela and Lazić, Sandra and Maksimović, Zlatko and Tanić, Nasta",
year = "2023",
abstract = "Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused COVID-19 pandemic. This coronavirus disease pandemic demonstrated the importance of diagnostic testing in disease outbreak monitoring and control. So, reliable and accurate testing for SARS-CoV-2 was the principal prerequisite for preventing the spread of COVID-19.
Methods: Real Time RT-PCR (RT-qPCR) unquestionably represent the most reliable, rapid and sensitive method for detection of SARS-CoV-2 RNA. However, there are numerous different assays, protocols, reagents, instruments and result analysis methods in use without certified standards, standardized RNA extraction and reporting procedures. Therefore, in practice, the reliability of RT-qPCR results depends on a number of parameters that include sample collection and processing, method of RNA extraction, choice of assay, efficiency of assay, choice of instrument, analysis method as well as operator intervention.
Results: Here we present comparative analyses of the efficiency and sensitivity of 10 different amplification assays, as well as the relevance of manual RNA extractions compared to automatic one. Our results revealed that manual viral RNA extraction should be a method of choice for high sensitivity. In addition, amplification assays targeting three SARS-CoV-2 genes are much more efficient from those targeting one.
Conclusion: Unfortunately, RT-qPCR is almost exclusively used as qualitative diagnostic test for SARSCoV-2. We think that the ideal testing regimen would involve not just qualitative detection of SARS-CoV-2 but reliable and meaningful quantitative reporting of viral load.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Diagnostic testing for SARS-COV-2 by Real-time RT-PCR",
number = "99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6328"
}

Tanić, N., Blagojević, D., Milanović, I., Imširović, M., Lazić, S., Maksimović, Z.,& Tanić, N.. (2023). Diagnostic testing for SARS-COV-2 by Real-time RT-PCR. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade.(99).
https://hdl.handle.net/21.15107/rcub_ibiss_6328

Tanić N, Blagojević D, Milanović I, Imširović M, Lazić S, Maksimović Z, Tanić N. Diagnostic testing for SARS-COV-2 by Real-time RT-PCR. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;(99).
https://hdl.handle.net/21.15107/rcub_ibiss_6328 .

Tanić, Nikola, Blagojević, Danijela, Milanović, Ivana, Imširović, Mirela, Lazić, Sandra, Maksimović, Zlatko, Tanić, Nasta, "Diagnostic testing for SARS-COV-2 by Real-time RT-PCR" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia, no. 99 (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_6328 .

TY  - CONF
AU  - Ademović, Nejla
AU  - Tanić, Nasta
AU  - Tomić, Tijana
AU  - Murganić, Blagoje
AU  - Milić, Marina
AU  - Tanić, Nikola
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6327
AB  - Introduction: Astrocytoma and glioblastoma are the most agressive type of brain tumor. Glioblastoma IDH wild-type is a primary tumor which develops de novo, while Astrocytoma IDH mutant progresses from lower grade tumors. They are characterized by high heterogeneity and resistance to therapy which develop as a consequence of accumulation of mutations that lead to genomic instability.
Methods: We analysed genomic instability in 66 patients with malign brain tumors using arbitrarily primed PCR as DNA profiling method. Comparing DNA profiles of tumor and normal (blood) tissues, we detected quantitative and qualitative differences. Quantitative differences are represented by different band intensities and correspond to chromosomal instability (CIN). Qualitative changes seen as band shifts represent microsatellite instability (MIN). We correlated frequencies of genomic instability with tumor gradus and histophatological data.
Results: In patients with Glioblastoma IDH wild-type, percentages of high total genomic instability, MIN and CIN were 65%, 32% and 57%, respectfully. In patients with Astrocytoma IDHmutant, percentages of high total genomic instability, MIN and CIN for gradus 3 were 45%, 36% and 72%, respectfully while they were 40%, 40% and 40%, for gradus 4. In patients with NOS (not otherwise specified glioblastoma) percentages are 50%, 50% and 70%, respectfully.
Conclusion: Our results show that Glioblastoma IDH wild-type and Astrocytoma IDH mutant gradus 3 have higher genomic instability, while it is lower in Astrocytoma IDH mutant gradus 4. These results are in line with evolutionary theory of origin of cancer. Genomic instability in NOS tumors could be used as a prognostic marker.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Detection of genomic instability in malignant brain tumors
SP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6327
ER  - 

@conference{
author = "Ademović, Nejla and Tanić, Nasta and Tomić, Tijana and Murganić, Blagoje and Milić, Marina and Tanić, Nikola",
year = "2023",
abstract = "Introduction: Astrocytoma and glioblastoma are the most agressive type of brain tumor. Glioblastoma IDH wild-type is a primary tumor which develops de novo, while Astrocytoma IDH mutant progresses from lower grade tumors. They are characterized by high heterogeneity and resistance to therapy which develop as a consequence of accumulation of mutations that lead to genomic instability.
Methods: We analysed genomic instability in 66 patients with malign brain tumors using arbitrarily primed PCR as DNA profiling method. Comparing DNA profiles of tumor and normal (blood) tissues, we detected quantitative and qualitative differences. Quantitative differences are represented by different band intensities and correspond to chromosomal instability (CIN). Qualitative changes seen as band shifts represent microsatellite instability (MIN). We correlated frequencies of genomic instability with tumor gradus and histophatological data.
Results: In patients with Glioblastoma IDH wild-type, percentages of high total genomic instability, MIN and CIN were 65%, 32% and 57%, respectfully. In patients with Astrocytoma IDHmutant, percentages of high total genomic instability, MIN and CIN for gradus 3 were 45%, 36% and 72%, respectfully while they were 40%, 40% and 40%, for gradus 4. In patients with NOS (not otherwise specified glioblastoma) percentages are 50%, 50% and 70%, respectfully.
Conclusion: Our results show that Glioblastoma IDH wild-type and Astrocytoma IDH mutant gradus 3 have higher genomic instability, while it is lower in Astrocytoma IDH mutant gradus 4. These results are in line with evolutionary theory of origin of cancer. Genomic instability in NOS tumors could be used as a prognostic marker.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Detection of genomic instability in malignant brain tumors",
pages = "98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6327"
}

Ademović, N., Tanić, N., Tomić, T., Murganić, B., Milić, M.,& Tanić, N.. (2023). Detection of genomic instability in malignant brain tumors. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 98.
https://hdl.handle.net/21.15107/rcub_ibiss_6327

Ademović N, Tanić N, Tomić T, Murganić B, Milić M, Tanić N. Detection of genomic instability in malignant brain tumors. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:98.
https://hdl.handle.net/21.15107/rcub_ibiss_6327 .

Ademović, Nejla, Tanić, Nasta, Tomić, Tijana, Murganić, Blagoje, Milić, Marina, Tanić, Nikola, "Detection of genomic instability in malignant brain tumors" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):98,
https://hdl.handle.net/21.15107/rcub_ibiss_6327 .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Bovan, Dijana
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mijatović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6267
AB  - Background: Shikonins are naturally occurring naphthoquinones found in the roots of several genera of the Boraginaceae family, widely known for their antiinflammatory, antioxidant, antimicrobial, and anticancer properties. This study aimed to investigate the antitumor potential of six shikonins isolated from the roots of Onosma visianii against highly aggressive rat glioma cell line C6 and to explore the mechanisms involved. Material and Methods: Cell viability was estimated by MTT and CV assays. Cell death, proliferation rate, and caspase activity were assessed using flow cytometric analysis of annexin V-FITC/propidium iodide, CFSE, and ApoStat staining, respectively. Fluorescent microscopy of propidium iodide-stained cells was employed for the detection of nuclear morphology. To evaluate the viability of detached cells, an acidic phosphatase assay was used. The cells’ property to adhere was assessed by cell adhesion assay while western blot was engaged to measure the expression of relevant proteins responsible for the observed phenomenon. Results and Conclusions: All examined shikonins dose-dependently decreased the viability of C6 cells, with compounds 5 and 6 being the most potent ones. Compound 5 had a more profound effect on the proliferation rate of C6 cells than compound 6, resulting in almost 70% of inhibition of cell division. Additionally, compound 5, but not compound 6 generated a significant number of early and late apoptotic cells in treated cultures as detected by flow cytometry. In collision with this, typical morphological signs of apoptotic cells were not observed, and fluorescent microscopy revealed only the presence of enlarged nuclei. This paradox was resolved by the discovery of massive detached cell presence, indicating that glioma cells underwent anoikis, a cell attachment-dependent programmed cell death, in response to treatment with both agents. Decreased ability of C6 cells to adhere to the extracellular matrix and compromised integrin signaling was further confirmed by adhesion assay and western blot, respectively. Interestingly, while compound 5 triggered caspase-mediated anoikis, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. This study represents the first proof of shikonin derivatives’ strong anticancer potential realized through the induction of anoikis of highly proliferative and invasive malignant glioma cells.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells
SP  - 98
EP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6267
ER  - 

@conference{
author = "Krajnović, Tamara and Bovan, Dijana and Vuković, Nenad L. and Vukić, Milena D. and Mijatović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Shikonins are naturally occurring naphthoquinones found in the roots of several genera of the Boraginaceae family, widely known for their antiinflammatory, antioxidant, antimicrobial, and anticancer properties. This study aimed to investigate the antitumor potential of six shikonins isolated from the roots of Onosma visianii against highly aggressive rat glioma cell line C6 and to explore the mechanisms involved. Material and Methods: Cell viability was estimated by MTT and CV assays. Cell death, proliferation rate, and caspase activity were assessed using flow cytometric analysis of annexin V-FITC/propidium iodide, CFSE, and ApoStat staining, respectively. Fluorescent microscopy of propidium iodide-stained cells was employed for the detection of nuclear morphology. To evaluate the viability of detached cells, an acidic phosphatase assay was used. The cells’ property to adhere was assessed by cell adhesion assay while western blot was engaged to measure the expression of relevant proteins responsible for the observed phenomenon. Results and Conclusions: All examined shikonins dose-dependently decreased the viability of C6 cells, with compounds 5 and 6 being the most potent ones. Compound 5 had a more profound effect on the proliferation rate of C6 cells than compound 6, resulting in almost 70% of inhibition of cell division. Additionally, compound 5, but not compound 6 generated a significant number of early and late apoptotic cells in treated cultures as detected by flow cytometry. In collision with this, typical morphological signs of apoptotic cells were not observed, and fluorescent microscopy revealed only the presence of enlarged nuclei. This paradox was resolved by the discovery of massive detached cell presence, indicating that glioma cells underwent anoikis, a cell attachment-dependent programmed cell death, in response to treatment with both agents. Decreased ability of C6 cells to adhere to the extracellular matrix and compromised integrin signaling was further confirmed by adhesion assay and western blot, respectively. Interestingly, while compound 5 triggered caspase-mediated anoikis, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. This study represents the first proof of shikonin derivatives’ strong anticancer potential realized through the induction of anoikis of highly proliferative and invasive malignant glioma cells.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells",
pages = "98-99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6267"
}

Krajnović, T., Bovan, D., Vuković, N. L., Vukić, M. D., Mijatović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2023). Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 98-99.
https://hdl.handle.net/21.15107/rcub_ibiss_6267

Krajnović T, Bovan D, Vuković NL, Vukić MD, Mijatović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:98-99.
https://hdl.handle.net/21.15107/rcub_ibiss_6267 .

Krajnović, Tamara, Bovan, Dijana, Vuković, Nenad L., Vukić, Milena D., Mijatović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):98-99,
https://hdl.handle.net/21.15107/rcub_ibiss_6267 .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandr
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6261
AB  - Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула.
AB  - Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке
T1  - Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment
SP  - 18
EP  - 19
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6261
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandr and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула., Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке, Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment",
pages = "18-19",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6261"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

Murganić, Blagoje, Kazimir, Aleksandr, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):18-19,
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandar
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6244
AB  - Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6244
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandar and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6244"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

Murganić, Blagoje, Kazimir, Aleksandar, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):95,
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Bovan, Dijana
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mihajlović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6237
AB  - Shikonin is a naphthoquinone found in the roots of plants of the Boraginaceae family and
is widely known for its numerous biological activities, including anticancer. In this study,
the antitumor mode of action of shikonin derivatives isolated from the roots of Onosma
visianii was investigated in mouse melanoma cell line B16. MTT and CV assays showed
that six examined shikonins decreased B16 cell viability in a dose-dependent manner, with
compounds 5 and 6 exhibiting the highest cytotoxic activity. This effect correlated with
caspase-mediated apoptosis, which was detected by flow cytometry and fluorescence
microscopy. In addition, CFSE staining revealed a strong blockage of cell division in
response to treatment, with a more profound effect of compound 6. The altered cell
morphology together with the loss of dividing potential upon exposure to both shikonins
implied reprogramming of the B16 cell phenotype. The absence of melanogenesis
enhancement coupled with an elevated level of myelin basic protein in response to
treatment with both tested agents suggested that the cells transdifferentiated into a
Schwann-like phenotype, with possible involvement of the autophagic process in this
conversion. Differentiation of malignant cells has become favourable in cancer treatment,
bearing in mind the phenomenon of apoptosis-induced proliferation. Hence, the specific
antitumor mode of action of shikonin derivatives on melanoma in vitro shown here
provides a good platform for new investigations of these promising natural compounds.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells
SP  - 96
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6237
ER  - 

@conference{
author = "Krajnović, Tamara and Bovan, Dijana and Vuković, Nenad L. and Vukić, Milena D. and Mihajlović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Shikonin is a naphthoquinone found in the roots of plants of the Boraginaceae family and
is widely known for its numerous biological activities, including anticancer. In this study,
the antitumor mode of action of shikonin derivatives isolated from the roots of Onosma
visianii was investigated in mouse melanoma cell line B16. MTT and CV assays showed
that six examined shikonins decreased B16 cell viability in a dose-dependent manner, with
compounds 5 and 6 exhibiting the highest cytotoxic activity. This effect correlated with
caspase-mediated apoptosis, which was detected by flow cytometry and fluorescence
microscopy. In addition, CFSE staining revealed a strong blockage of cell division in
response to treatment, with a more profound effect of compound 6. The altered cell
morphology together with the loss of dividing potential upon exposure to both shikonins
implied reprogramming of the B16 cell phenotype. The absence of melanogenesis
enhancement coupled with an elevated level of myelin basic protein in response to
treatment with both tested agents suggested that the cells transdifferentiated into a
Schwann-like phenotype, with possible involvement of the autophagic process in this
conversion. Differentiation of malignant cells has become favourable in cancer treatment,
bearing in mind the phenomenon of apoptosis-induced proliferation. Hence, the specific
antitumor mode of action of shikonin derivatives on melanoma in vitro shown here
provides a good platform for new investigations of these promising natural compounds.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells",
pages = "96",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6237"
}

Krajnović, T., Bovan, D., Vuković, N. L., Vukić, M. D., Mihajlović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2023). Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells. in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 96.
https://hdl.handle.net/21.15107/rcub_ibiss_6237

Krajnović T, Bovan D, Vuković NL, Vukić MD, Mihajlović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells. in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:96.
https://hdl.handle.net/21.15107/rcub_ibiss_6237 .

Krajnović, Tamara, Bovan, Dijana, Vuković, Nenad L., Vukić, Milena D., Mihajlović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells" in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):96,
https://hdl.handle.net/21.15107/rcub_ibiss_6237 .

TY  - CONF
AU  - Ademović, Nejla
AU  - Tomić, Tijana
AU  - Tanić, Nasta
AU  - Milić, Marina
AU  - Rakić, Miodrag
AU  - Tanić, Nikola
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6234
AB  - Introduction. Glioblastoma and Astrocytoma are diffuse malignant brain tumors and characterized as the most aggressive and invasive brain cancers. Glioblastoma IDH wild-type is a primary brain tumour that develops de novo, and Astrocytoma IDH mutant is a secondary tumour which arises by progression from lower tumour grades. They are characterized by poor survival, resistance to therapy and poor prognosis which develops as a consequence of genomic instability. Genomic instability also contributes to tumour heterogeneity and provides the genomic diversity necessary for selection.
Materials and methods. 31 patients with Glioblastoma IDH wild-type and Astrocytoma IDH mutant, grade 3 and 4, were analysed for the presence of genomic instability using AP-PCR, DNA profiling method. Comparing DNA profiles between tumour tissue and normal tissue (blood) of the same patient, we detected qualitative and quantitative changes. Qualitative changes are detected as the presence and absence of bands and are the manifestation of microsatellite instability (MIN). Quantitative changes are the representation of chromosomal instability (CIN) and are detected as differences in the intensity of bands. Survival analyses were performed using Kaplan & Maier test for survival data in relation to different histological tumour type and genomic instability. Statistical differences were considered significant for p≤ 0,05.
Results. Patients with Glioblastoma IDH wild-type have significantly shorter survival compared to other histological types (p=0,025). For each histological type that we analysed and each type of instability, MIN, CIN and total genomic instability, two groups of patients were made - those with high and low instability. Patients with Glioblastoma IDH wild-type that have low total genomic instability have significantly shorter survival (p=0,045) compared to other analysed types of brain cancer. Patients with Astrocytoma IDH mutant grade 4 who have high total genomic instability and high CIN have significantly shorter survival (p=0,018, p=0,007 respectfully).
Conclusion. Patients with Glioblastoma IDH wild-type have shorter survival which makes this tumour the most aggressive and malignat of all analysed tumours. Our results show that low genomic instability in Glioblastoma IDH wild-type and high genomic instability lead by high CIN in Astrocytoma IDH mutant, gradus 4 contribute to shorter survival, which makes genomic instability a potential good prognostic marker.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Genomic instability as a prognostic marker in malignant brain cancer
SP  - 90
EP  - 91
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6234
ER  - 

@conference{
author = "Ademović, Nejla and Tomić, Tijana and Tanić, Nasta and Milić, Marina and Rakić, Miodrag and Tanić, Nikola",
year = "2023",
abstract = "Introduction. Glioblastoma and Astrocytoma are diffuse malignant brain tumors and characterized as the most aggressive and invasive brain cancers. Glioblastoma IDH wild-type is a primary brain tumour that develops de novo, and Astrocytoma IDH mutant is a secondary tumour which arises by progression from lower tumour grades. They are characterized by poor survival, resistance to therapy and poor prognosis which develops as a consequence of genomic instability. Genomic instability also contributes to tumour heterogeneity and provides the genomic diversity necessary for selection.
Materials and methods. 31 patients with Glioblastoma IDH wild-type and Astrocytoma IDH mutant, grade 3 and 4, were analysed for the presence of genomic instability using AP-PCR, DNA profiling method. Comparing DNA profiles between tumour tissue and normal tissue (blood) of the same patient, we detected qualitative and quantitative changes. Qualitative changes are detected as the presence and absence of bands and are the manifestation of microsatellite instability (MIN). Quantitative changes are the representation of chromosomal instability (CIN) and are detected as differences in the intensity of bands. Survival analyses were performed using Kaplan & Maier test for survival data in relation to different histological tumour type and genomic instability. Statistical differences were considered significant for p≤ 0,05.
Results. Patients with Glioblastoma IDH wild-type have significantly shorter survival compared to other histological types (p=0,025). For each histological type that we analysed and each type of instability, MIN, CIN and total genomic instability, two groups of patients were made - those with high and low instability. Patients with Glioblastoma IDH wild-type that have low total genomic instability have significantly shorter survival (p=0,045) compared to other analysed types of brain cancer. Patients with Astrocytoma IDH mutant grade 4 who have high total genomic instability and high CIN have significantly shorter survival (p=0,018, p=0,007 respectfully).
Conclusion. Patients with Glioblastoma IDH wild-type have shorter survival which makes this tumour the most aggressive and malignat of all analysed tumours. Our results show that low genomic instability in Glioblastoma IDH wild-type and high genomic instability lead by high CIN in Astrocytoma IDH mutant, gradus 4 contribute to shorter survival, which makes genomic instability a potential good prognostic marker.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Genomic instability as a prognostic marker in malignant brain cancer",
pages = "90-91",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6234"
}

Ademović, N., Tomić, T., Tanić, N., Milić, M., Rakić, M.,& Tanić, N.. (2023). Genomic instability as a prognostic marker in malignant brain cancer. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 90-91.
https://hdl.handle.net/21.15107/rcub_ibiss_6234

Ademović N, Tomić T, Tanić N, Milić M, Rakić M, Tanić N. Genomic instability as a prognostic marker in malignant brain cancer. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:90-91.
https://hdl.handle.net/21.15107/rcub_ibiss_6234 .

Ademović, Nejla, Tomić, Tijana, Tanić, Nasta, Milić, Marina, Rakić, Miodrag, Tanić, Nikola, "Genomic instability as a prognostic marker in malignant brain cancer" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):90-91,
https://hdl.handle.net/21.15107/rcub_ibiss_6234 .

TY  - JOUR
AU  - Jelača, Sanja
AU  - Dajić-Stevanović, Zora
AU  - Vuković, Nenad
AU  - Kolašinac, Stefan
AU  - Trendafilova, Antoaneta
AU  - Nedialkov, Paraskev
AU  - Stanković, Miroslava
AU  - Tanić, Nasta
AU  - Tanić, Nikola
AU  - Acović, Aleksandar
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5300
AB  - Alchemilla vulgaris L. (lady’s mantle) was used for centuries in Europe and Balkan countries for treatments of numerous conditions and diseases of the reproductive system, yet some of the biological activities of lady’s mantle have been poorly studied and neglected. The present study aimed to estimate the potential of A. vulgaris ethanolic extract from Southeast Serbia to prevent and suppress tumor development in vitro, validated by antioxidant, genoprotective, and cytotoxic properties. A total of 45 compounds were detected by UHPLC–HRMS analysis in A. vulgaris ethanolic extract. Measurement of antioxidant activity revealed the significant potential of the tested extract to scavenge free radicals. In addition, the analysis of micronuclei showed an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes. A. vulgaris extract strongly suppressed the growth of human cell lines derived from different types of tumors (MCF-7, A375, A549, and HCT116). The observed antitumor effect is realized through the blockade of cell division, caspase-dependent apoptosis, and autophagic cell death. Our study has shown that Alchemilla vulgaris L. is a valuable source of bioactive compounds able to protect the subcellular structure from damage, thus preventing tumorigenesis as well as suppressing tumor cell growth.
PB  - Basel: MDPI
T2  - Molecules
T1  - Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro
IS  - 23
VL  - 27
DO  - 10.3390/molecules27238113
SP  - 8113
ER  - 

@article{
author = "Jelača, Sanja and Dajić-Stevanović, Zora and Vuković, Nenad and Kolašinac, Stefan and Trendafilova, Antoaneta and Nedialkov, Paraskev and Stanković, Miroslava and Tanić, Nasta and Tanić, Nikola and Acović, Aleksandar and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Alchemilla vulgaris L. (lady’s mantle) was used for centuries in Europe and Balkan countries for treatments of numerous conditions and diseases of the reproductive system, yet some of the biological activities of lady’s mantle have been poorly studied and neglected. The present study aimed to estimate the potential of A. vulgaris ethanolic extract from Southeast Serbia to prevent and suppress tumor development in vitro, validated by antioxidant, genoprotective, and cytotoxic properties. A total of 45 compounds were detected by UHPLC–HRMS analysis in A. vulgaris ethanolic extract. Measurement of antioxidant activity revealed the significant potential of the tested extract to scavenge free radicals. In addition, the analysis of micronuclei showed an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes. A. vulgaris extract strongly suppressed the growth of human cell lines derived from different types of tumors (MCF-7, A375, A549, and HCT116). The observed antitumor effect is realized through the blockade of cell division, caspase-dependent apoptosis, and autophagic cell death. Our study has shown that Alchemilla vulgaris L. is a valuable source of bioactive compounds able to protect the subcellular structure from damage, thus preventing tumorigenesis as well as suppressing tumor cell growth.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro",
number = "23",
volume = "27",
doi = "10.3390/molecules27238113",
pages = "8113"
}

Jelača, S., Dajić-Stevanović, Z., Vuković, N., Kolašinac, S., Trendafilova, A., Nedialkov, P., Stanković, M., Tanić, N., Tanić, N., Acović, A., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro. in Molecules
Basel: MDPI., 27(23), 8113.
https://doi.org/10.3390/molecules27238113

Jelača S, Dajić-Stevanović Z, Vuković N, Kolašinac S, Trendafilova A, Nedialkov P, Stanković M, Tanić N, Tanić N, Acović A, Mijatović S, Maksimović-Ivanić D. Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro. in Molecules. 2022;27(23):8113.
doi:10.3390/molecules27238113 .

Jelača, Sanja, Dajić-Stevanović, Zora, Vuković, Nenad, Kolašinac, Stefan, Trendafilova, Antoaneta, Nedialkov, Paraskev, Stanković, Miroslava, Tanić, Nasta, Tanić, Nikola, Acović, Aleksandar, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro" in Molecules, 27, no. 23 (2022):8113,
https://doi.org/10.3390/molecules27238113 . .

TY  - JOUR
AU  - Su, Guo-Zhu
AU  - Wang, Shang-Yi
AU  - Yang, Xiu-Ying
AU  - Stevanović, Zora Dajić
AU  - Li, Na
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Yu, Shi-Shan
AU  - Li, Yong
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5165
AB  - Five undescribed dihydroflavonoid glycoside derivatives, namely albvisosides A‒E, together with two known compounds were isolated from the roots and stem leaves of Viscum album L. var. album. (European mistletoe). Their structures were determined by HRESIMS, 1D and 2D NMR, and ECD analysis. Albvisoside B exhibits significant inhibitory effect on hepatic lipid accumulation in HepG2 cells at very low concentrations (EC50: 0.7 nM). Using proteome integral solubility alteration assay, the direct targets or downstream effectors of albvisoside B were elucidated. As a result, 97 proteins were identified based on ligand-induced alterations in the protein thermal stability. Bioinformatics analysis indicated that albvisoside B primarily ameliorated oleic acid-induced lipid accumulation by regulating the selenoamino acids metabolism signaling pathway. RPL3, ADAM17, and RPL14 were likely to be involved in mediating the lipid-lowering effect of albvisoside B.
PB  - Oxford: Pergamon-Elsevier Science Ltd
T2  - Phytochemistry
T1  - Dihydroflavonoid glycosides from Viscum album and their inhibitory effects on hepatic lipid accumulation and target identification.
VL  - 204
DO  - 10.1016/j.phytochem.2022.113458
SP  - 113458
ER  - 

@article{
author = "Su, Guo-Zhu and Wang, Shang-Yi and Yang, Xiu-Ying and Stevanović, Zora Dajić and Li, Na and Tanić, Nikola and Arsenijević, Nebojša and Yu, Shi-Shan and Li, Yong",
year = "2022",
abstract = "Five undescribed dihydroflavonoid glycoside derivatives, namely albvisosides A‒E, together with two known compounds were isolated from the roots and stem leaves of Viscum album L. var. album. (European mistletoe). Their structures were determined by HRESIMS, 1D and 2D NMR, and ECD analysis. Albvisoside B exhibits significant inhibitory effect on hepatic lipid accumulation in HepG2 cells at very low concentrations (EC50: 0.7 nM). Using proteome integral solubility alteration assay, the direct targets or downstream effectors of albvisoside B were elucidated. As a result, 97 proteins were identified based on ligand-induced alterations in the protein thermal stability. Bioinformatics analysis indicated that albvisoside B primarily ameliorated oleic acid-induced lipid accumulation by regulating the selenoamino acids metabolism signaling pathway. RPL3, ADAM17, and RPL14 were likely to be involved in mediating the lipid-lowering effect of albvisoside B.",
publisher = "Oxford: Pergamon-Elsevier Science Ltd",
journal = "Phytochemistry",
title = "Dihydroflavonoid glycosides from Viscum album and their inhibitory effects on hepatic lipid accumulation and target identification.",
volume = "204",
doi = "10.1016/j.phytochem.2022.113458",
pages = "113458"
}

Su, G., Wang, S., Yang, X., Stevanović, Z. D., Li, N., Tanić, N., Arsenijević, N., Yu, S.,& Li, Y.. (2022). Dihydroflavonoid glycosides from Viscum album and their inhibitory effects on hepatic lipid accumulation and target identification.. in Phytochemistry
Oxford: Pergamon-Elsevier Science Ltd., 204, 113458.
https://doi.org/10.1016/j.phytochem.2022.113458

Su G, Wang S, Yang X, Stevanović ZD, Li N, Tanić N, Arsenijević N, Yu S, Li Y. Dihydroflavonoid glycosides from Viscum album and their inhibitory effects on hepatic lipid accumulation and target identification.. in Phytochemistry. 2022;204:113458.
doi:10.1016/j.phytochem.2022.113458 .

Su, Guo-Zhu, Wang, Shang-Yi, Yang, Xiu-Ying, Stevanović, Zora Dajić, Li, Na, Tanić, Nikola, Arsenijević, Nebojša, Yu, Shi-Shan, Li, Yong, "Dihydroflavonoid glycosides from Viscum album and their inhibitory effects on hepatic lipid accumulation and target identification." in Phytochemistry, 204 (2022):113458,
https://doi.org/10.1016/j.phytochem.2022.113458 . .

TY  - CONF
AU  - Tanić, Nikola
AU  - Tanić, Nasta
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5772
AB  - Cancer development is a multistage process that results from an accumulation of
mutations. Since spontaneous mutation rates in human cells are considerably lower
than the large number of mutations observed in cancer cells, cancer cells must be
a manifestation of mutator phenotype. The mutator phenotype, also referred to as
genomic instability, designates the increased mutation rate that occurs in neoplastic
cells. The induction of genomic instability phenotype is emerging to be a crucial
early event in carcinogenesis that enables an initiated cell to evolve into a cancer cell
by achieving a greater proliferative capacity and genetic plasticity, which can overcome
host immunological resistance, localized toxic environments and a suboptimal
supply of micronutrients. Three distinct forms of genomic instability have been
identified, microsatellite instability (MIN), chromosomal instability (CIN) and single
nucleotide instability (SNI). It is of great importance for the determination of
therapy and for therapy outcome, which form of instability is present in cancer
cells. Is there are a way to determine the form of instability and measure it in relatively
simple one step procedure and at low cost? Yes, AP-PCR is a PCR-based DNA
fingerprinting method for DNA profiling that utilizes arbitrarily chosen primers to
co-amplify multiple and independent sequences under low stringency conditions
during the first cycles. The unbiased nature of AP-PCR profiling allows for the
screening of anonymous regions of a genome without any prior knowledge of its
structure and provides information about two distinct types of DNA alterations.
These alterations represent accumulation of changes in DNA sequence (qualitative
changes – MIN phenotype) that manifest as mobility shifts in the banding pattern
while amplifications or deletions of existing chromosomal material (quantitative
changes – CIN phenotype) are evident as altered band intensities in the banding
pattern. We applied AP-PCR to measure genomic instability in samples of patients
with Non-Small Cell Lung Cancer, Anaplastic Astrocytomas, Glioblastoma Multiforme,
Head and Neck Squamous Cell Carcinomas and their premalignant lesions leukoplakias. Moreover, we identified some unique genetic alterations that has never
been associated with this types of cancer before.
AB  - Канцерогенеза је вишестепени процес, последица акумулације мутација. Како
је стопа спонтаних мутација у хуманим ћелијама знатно нижа од великог броја
мутација уочених у ћелијама рака, логична је претпоставка да су туморске ћелије
манифестација мутатор фенотипа. Мутатор фенотип, који је последица геномске
нестабилности, означава повећану стопу мутације која се јавља у неопластичним
ћелијама. Индукција мутатор фенотипа, геномске нестабилности, је кључни рани
догађај у процесу карциногенезе који омогућава иницираној ћелији да еволуира
у канцер ћелију постизањем већег пролиферативног капацитета и генетске пластичности, која може превазићи имунолошки одговор домаћина, локализована
токсична окружења и субоптимално снабдевање микронутријентима. Идентификована су три различита облика геномске нестабилности, микросателитска
нестабилност (МИН), хромозомска нестабилност (ЦИН) и нестабилност једног
нуклеотида (СНИ). За одређивање терапијског протокола и исход болест од суштинског је значаја који облик нестабилности је присутан у неопластичним ћелијама. Да ли постоји начин да се, у једном кораку са релативно једноставном
процедуром и по релативно ниској цени, утврди облик и измери степен геномске
нестабилности?Да, ланчана реакција полимеразе са арбитрарним прајмерима (АП-ПЦР) је метода ДНК фингерпринта (отиска прстију) заснована на модификованој варијанти
ПЦРа која се изводи са произвољно изабраним амплимерима за ко-амплификацију вишеструких и независних ДНК секвенци под условима смањене специфичности хибридизације током првих циклуса. Крајњи резултат овако дизајниране
реакције је генерисање специфичног ДНК профила, Непристрасна природа АП-
ПЦР профилисања омогућава скрининг анонимних региона генома без икаквог
претходног знања о његовој структури и пружа информације о две различите врсте промена на ДНК молекулу. Ове промене представљају акумулацију мутација
у ДНК секвенцама (квалитативне промене – МИН фенотип) које се манифестују
као промене покретљивости у обрасцу трака, док су амплификације или делеције постојећег хромозомског материјала (квантитативне промене – ЦИН фенотип)
видљиве као измењени интензитети трака у датом обрасцу. Ми смо применили
АП-ПЦР профилисање за идентификовање и мерење степена геномске нестабилности у узорцима пацијената са неситноћелијским карциномом плућа, анапластичним астроцитомом, глиобластомом мултиформе, карциномом сквамозних
ћелија главе и врата и њиховим премалигним лезијама леукоплакијама. На крају, идентификовали смо неке јединствене генетичке промене које никада раније
нису биле повезане са овим типовима канцера.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - DNA profiling in cancer research- diagnostic and prognostic value
T1  - ДНК профилисање у истраживањима рака- дијагностички и прогностички значај
SP  - 120
EP  - 123
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5772
ER  - 

@conference{
author = "Tanić, Nikola and Tanić, Nasta",
year = "2022",
abstract = "Cancer development is a multistage process that results from an accumulation of
mutations. Since spontaneous mutation rates in human cells are considerably lower
than the large number of mutations observed in cancer cells, cancer cells must be
a manifestation of mutator phenotype. The mutator phenotype, also referred to as
genomic instability, designates the increased mutation rate that occurs in neoplastic
cells. The induction of genomic instability phenotype is emerging to be a crucial
early event in carcinogenesis that enables an initiated cell to evolve into a cancer cell
by achieving a greater proliferative capacity and genetic plasticity, which can overcome
host immunological resistance, localized toxic environments and a suboptimal
supply of micronutrients. Three distinct forms of genomic instability have been
identified, microsatellite instability (MIN), chromosomal instability (CIN) and single
nucleotide instability (SNI). It is of great importance for the determination of
therapy and for therapy outcome, which form of instability is present in cancer
cells. Is there are a way to determine the form of instability and measure it in relatively
simple one step procedure and at low cost? Yes, AP-PCR is a PCR-based DNA
fingerprinting method for DNA profiling that utilizes arbitrarily chosen primers to
co-amplify multiple and independent sequences under low stringency conditions
during the first cycles. The unbiased nature of AP-PCR profiling allows for the
screening of anonymous regions of a genome without any prior knowledge of its
structure and provides information about two distinct types of DNA alterations.
These alterations represent accumulation of changes in DNA sequence (qualitative
changes – MIN phenotype) that manifest as mobility shifts in the banding pattern
while amplifications or deletions of existing chromosomal material (quantitative
changes – CIN phenotype) are evident as altered band intensities in the banding
pattern. We applied AP-PCR to measure genomic instability in samples of patients
with Non-Small Cell Lung Cancer, Anaplastic Astrocytomas, Glioblastoma Multiforme,
Head and Neck Squamous Cell Carcinomas and their premalignant lesions leukoplakias. Moreover, we identified some unique genetic alterations that has never
been associated with this types of cancer before., Канцерогенеза је вишестепени процес, последица акумулације мутација. Како
је стопа спонтаних мутација у хуманим ћелијама знатно нижа од великог броја
мутација уочених у ћелијама рака, логична је претпоставка да су туморске ћелије
манифестација мутатор фенотипа. Мутатор фенотип, који је последица геномске
нестабилности, означава повећану стопу мутације која се јавља у неопластичним
ћелијама. Индукција мутатор фенотипа, геномске нестабилности, је кључни рани
догађај у процесу карциногенезе који омогућава иницираној ћелији да еволуира
у канцер ћелију постизањем већег пролиферативног капацитета и генетске пластичности, која може превазићи имунолошки одговор домаћина, локализована
токсична окружења и субоптимално снабдевање микронутријентима. Идентификована су три различита облика геномске нестабилности, микросателитска
нестабилност (МИН), хромозомска нестабилност (ЦИН) и нестабилност једног
нуклеотида (СНИ). За одређивање терапијског протокола и исход болест од суштинског је значаја који облик нестабилности је присутан у неопластичним ћелијама. Да ли постоји начин да се, у једном кораку са релативно једноставном
процедуром и по релативно ниској цени, утврди облик и измери степен геномске
нестабилности?Да, ланчана реакција полимеразе са арбитрарним прајмерима (АП-ПЦР) је метода ДНК фингерпринта (отиска прстију) заснована на модификованој варијанти
ПЦРа која се изводи са произвољно изабраним амплимерима за ко-амплификацију вишеструких и независних ДНК секвенци под условима смањене специфичности хибридизације током првих циклуса. Крајњи резултат овако дизајниране
реакције је генерисање специфичног ДНК профила, Непристрасна природа АП-
ПЦР профилисања омогућава скрининг анонимних региона генома без икаквог
претходног знања о његовој структури и пружа информације о две различите врсте промена на ДНК молекулу. Ове промене представљају акумулацију мутација
у ДНК секвенцама (квалитативне промене – МИН фенотип) које се манифестују
као промене покретљивости у обрасцу трака, док су амплификације или делеције постојећег хромозомског материјала (квантитативне промене – ЦИН фенотип)
видљиве као измењени интензитети трака у датом обрасцу. Ми смо применили
АП-ПЦР профилисање за идентификовање и мерење степена геномске нестабилности у узорцима пацијената са неситноћелијским карциномом плућа, анапластичним астроцитомом, глиобластомом мултиформе, карциномом сквамозних
ћелија главе и врата и њиховим премалигним лезијама леукоплакијама. На крају, идентификовали смо неке јединствене генетичке промене које никада раније
нису биле повезане са овим типовима канцера.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "DNA profiling in cancer research- diagnostic and prognostic value, ДНК профилисање у истраживањима рака- дијагностички и прогностички значај",
pages = "120-123",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5772"
}

Tanić, N.,& Tanić, N.. (2022). DNA profiling in cancer research- diagnostic and prognostic value. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 120-123.
https://hdl.handle.net/21.15107/rcub_ibiss_5772

Tanić N, Tanić N. DNA profiling in cancer research- diagnostic and prognostic value. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:120-123.
https://hdl.handle.net/21.15107/rcub_ibiss_5772 .

Tanić, Nikola, Tanić, Nasta, "DNA profiling in cancer research- diagnostic and prognostic value" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):120-123,
https://hdl.handle.net/21.15107/rcub_ibiss_5772 .

TY  - CONF
AU  - Tanić, Nikola
AU  - Dramićanin, Tatjana
AU  - Milovanović, Zorka
AU  - Nedeljković, Milica
AU  - Tomić, Tijana
AU  - Ademović, Nejla
AU  - Murganić, Blagoje
AU  - Tanic, Nasta
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5773
AB  - Breast cancer (BC) is the most frequent type of malignancy and the leading cause
of cancer related death among women worldwide. More than 70% of all diagnosed invasive
BCs express steroid receptors and, as such, are subjected to endocrine therapy.
BC is exceptionally heterogeneous disease and therefore distinct treatment modalities
are necessary to address these differences. The aim of our study was to investigate
the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC
response to different treatment modalities, as well as, their possible cooperation, on
post-operative BC samples. To that end the patients were classified, based on applied
adjuvant therapy, into four distinct groups: those that received hormonal therapy
(HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal
therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic
therapies that exclude HT (for example CHT or H). Functional inactivation of
TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and
hypermethylatyon analysis. Our results revealed that TP53 gene was altered in 63 out
of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower,
54 out of 90 (60%) patients had inactivated PTEN. Simultaneous inactivation was
detected in 43 tested samples (48%) with significant association between two analyzed
TSGs. Further, we found that TP53 status has significant influence on patients’
therapy response. Patients with wild type TP53 show significantly better therapy response
regardless of the type of therapy, compared to carriers of altered p53 gene. In
support of this we showed that hormonally treated women with intact (wt) TP53 gene
had significantly longer survival rate (p=0.000001) when compared to: (i) hormonally
treated women with aberrant TP53gene, (ii) women with intact (wt) p53 subjected to
any of remaining three therapy combinations, and (iii) women with altered TP53 that
belong to second (HT/CHT), third (HT/CHT/H) or forth (systemic Th that exclude
HT) therapy group. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association
was found between the type of applied therapy and simultaneous alterations of these
two TSGs (p=0.00001).
AB  - Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од канцера код
жена широм света. Више од 70% свих дијагностикованих инвазивних карцинома
дојке експримира стероидне рецепторе и као такви су подобни за ендокрину терапију. Канцер дојке је изузетно хетерогена болест и стога су неопходни различити модалитети лечења да би се превазишле ове разлике. Циљ нашег истраживања
био је да се испита утицај инактивације ТП53 и ПТЕН тумор супресорских гена
(ТСГ) у одговору на различите модалитете лечења на постоперативним узорцима
карцинома дојке. Са тим циљем пацијенткиње су класификоване, на основу примењене ађувантне терапије, у четири различите групе: оне које су примале само
хормонску терапију (ХТ), хормонску терапију у комбинацији са хемиотерапијом
(ХТ/ЦХТ), хормонску терапију у комбинацији са хемиотерапијом и биолошком
терапијом (ХТ). /ЦХТ/Х) и друге системске терапије које искључују ХТ (на пример ЦХТ или Х). Функционална инактивација ТП53 и ПТЕН тумор супресора
је студирана анализом мутационог статуса, губитка хетерозиготности (ЛОХ) и
анализом метилационог статуса. Наши резултати су показали да је ТП53 ген измењен код 63 од 90 узорака (70%), док је учесталост промена ПТЕН гена била
нешто нижа, 54 од 90 (60%) пацијената је имало инактивиран ПТЕН. Симултана
инактивација је детектована у 43 тестирана узорка (48%) са значајном повезаношћу инактивације два анализирана тумор супресор гена.
Даље, показали смо да статус ТП53 има значајан утицај на одговор пацијената
на терапију. Пацијенти са дивљим типом (wt) ТП53 показују значајно бољи терапијски одговор без обзира на врсту терапије, у поређењу са носиоцима измењеног TП53. У прилог овоме показали смо да су хормонски лечене жене са интактним (wt) ТП53 геном имале значајно већу стопу преживљавања (п=0,000001) у
поређењу са: (1) женама леченим хормонсом теерапијом са аберантним ТП53 геном, (2) женама са интактним (wt) TП53 подвргнутим било којој од преостале три терапијске комбинације, и (3) женама са измењеним ТП53 које припадају другој
(ХТ/ЦХТ), трећој (ХТ/ЦХТ/Х) или четвртој (системска терапија која искључује ХТ) терапијској групи. Супротно овоме, нисмо утврдили значајну асоцијацију
између мутационог статуса ПТЕН-а и различитих модалитета лечења. Међутим,
утврђена је значајна повезаност између врсте примењене терапије и истовремених промена ова два тумор супресор гена (п=0,00001).
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities
T1  - Улога ТП53 и ПТЕН тумор супресор гена у одговору на различите модалитете терапије канцера дојке
SP  - 94
EP  - 97
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5773
ER  - 

@conference{
author = "Tanić, Nikola and Dramićanin, Tatjana and Milovanović, Zorka and Nedeljković, Milica and Tomić, Tijana and Ademović, Nejla and Murganić, Blagoje and Tanic, Nasta",
year = "2022",
abstract = "Breast cancer (BC) is the most frequent type of malignancy and the leading cause
of cancer related death among women worldwide. More than 70% of all diagnosed invasive
BCs express steroid receptors and, as such, are subjected to endocrine therapy.
BC is exceptionally heterogeneous disease and therefore distinct treatment modalities
are necessary to address these differences. The aim of our study was to investigate
the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC
response to different treatment modalities, as well as, their possible cooperation, on
post-operative BC samples. To that end the patients were classified, based on applied
adjuvant therapy, into four distinct groups: those that received hormonal therapy
(HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal
therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic
therapies that exclude HT (for example CHT or H). Functional inactivation of
TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and
hypermethylatyon analysis. Our results revealed that TP53 gene was altered in 63 out
of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower,
54 out of 90 (60%) patients had inactivated PTEN. Simultaneous inactivation was
detected in 43 tested samples (48%) with significant association between two analyzed
TSGs. Further, we found that TP53 status has significant influence on patients’
therapy response. Patients with wild type TP53 show significantly better therapy response
regardless of the type of therapy, compared to carriers of altered p53 gene. In
support of this we showed that hormonally treated women with intact (wt) TP53 gene
had significantly longer survival rate (p=0.000001) when compared to: (i) hormonally
treated women with aberrant TP53gene, (ii) women with intact (wt) p53 subjected to
any of remaining three therapy combinations, and (iii) women with altered TP53 that
belong to second (HT/CHT), third (HT/CHT/H) or forth (systemic Th that exclude
HT) therapy group. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association
was found between the type of applied therapy and simultaneous alterations of these
two TSGs (p=0.00001)., Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од канцера код
жена широм света. Више од 70% свих дијагностикованих инвазивних карцинома
дојке експримира стероидне рецепторе и као такви су подобни за ендокрину терапију. Канцер дојке је изузетно хетерогена болест и стога су неопходни различити модалитети лечења да би се превазишле ове разлике. Циљ нашег истраживања
био је да се испита утицај инактивације ТП53 и ПТЕН тумор супресорских гена
(ТСГ) у одговору на различите модалитете лечења на постоперативним узорцима
карцинома дојке. Са тим циљем пацијенткиње су класификоване, на основу примењене ађувантне терапије, у четири различите групе: оне које су примале само
хормонску терапију (ХТ), хормонску терапију у комбинацији са хемиотерапијом
(ХТ/ЦХТ), хормонску терапију у комбинацији са хемиотерапијом и биолошком
терапијом (ХТ). /ЦХТ/Х) и друге системске терапије које искључују ХТ (на пример ЦХТ или Х). Функционална инактивација ТП53 и ПТЕН тумор супресора
је студирана анализом мутационог статуса, губитка хетерозиготности (ЛОХ) и
анализом метилационог статуса. Наши резултати су показали да је ТП53 ген измењен код 63 од 90 узорака (70%), док је учесталост промена ПТЕН гена била
нешто нижа, 54 од 90 (60%) пацијената је имало инактивиран ПТЕН. Симултана
инактивација је детектована у 43 тестирана узорка (48%) са значајном повезаношћу инактивације два анализирана тумор супресор гена.
Даље, показали смо да статус ТП53 има значајан утицај на одговор пацијената
на терапију. Пацијенти са дивљим типом (wt) ТП53 показују значајно бољи терапијски одговор без обзира на врсту терапије, у поређењу са носиоцима измењеног TП53. У прилог овоме показали смо да су хормонски лечене жене са интактним (wt) ТП53 геном имале значајно већу стопу преживљавања (п=0,000001) у
поређењу са: (1) женама леченим хормонсом теерапијом са аберантним ТП53 геном, (2) женама са интактним (wt) TП53 подвргнутим било којој од преостале три терапијске комбинације, и (3) женама са измењеним ТП53 које припадају другој
(ХТ/ЦХТ), трећој (ХТ/ЦХТ/Х) или четвртој (системска терапија која искључује ХТ) терапијској групи. Супротно овоме, нисмо утврдили значајну асоцијацију
између мутационог статуса ПТЕН-а и различитих модалитета лечења. Међутим,
утврђена је значајна повезаност између врсте примењене терапије и истовремених промена ова два тумор супресор гена (п=0,00001).",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities, Улога ТП53 и ПТЕН тумор супресор гена у одговору на различите модалитете терапије канцера дојке",
pages = "94-97",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5773"
}

Tanić, N., Dramićanin, T., Milovanović, Z., Nedeljković, M., Tomić, T., Ademović, N., Murganić, B.,& Tanic, N.. (2022). The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 94-97.
https://hdl.handle.net/21.15107/rcub_ibiss_5773

Tanić N, Dramićanin T, Milovanović Z, Nedeljković M, Tomić T, Ademović N, Murganić B, Tanic N. The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:94-97.
https://hdl.handle.net/21.15107/rcub_ibiss_5773 .

Tanić, Nikola, Dramićanin, Tatjana, Milovanović, Zorka, Nedeljković, Milica, Tomić, Tijana, Ademović, Nejla, Murganić, Blagoje, Tanic, Nasta, "The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):94-97,
https://hdl.handle.net/21.15107/rcub_ibiss_5773 .

TY  - CONF
AU  - Nedeljković, Milica
AU  - Stojišić, Jelena
AU  - Tanić, Nasta
AU  - Murganić, Blagoje
AU  - Tomić, Tijana
AU  - Ademović, Nejla
AU  - Tanić, Nikola
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5771
AB  - Lung cancer is the most frequently diagnosed and lethal malignancy in the
world. Lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC)
are two subtypes of non-small cell lung cancer (NSCLC) which differ markedly in
key clinical and biological features. Despite this, they are usually treated similarly.
It is imperative to elucidate the mechanisms behind these differences in order to
implement better therapeutic modalities and biomarkers. Increased expression of
carbonic anhydrases Ca9 and Ca12 was observed in a broad array of tumors. Ca9
and Ca12 have a crucial role in the maintenance of the neutral intracellular pH and
the acidic extracellular microenvironment which stimulates the proliferation and
metastasis of tumor cells. Our aim was to detect possible difference in expression
level of Ca9 and Ca12 in LAC and LSCC, and to investigate whether the expression
of Ca9 and Ca12 was associated with the clinical course and outcome. We evaluated
the Ca9 and Ca12 expressions in 71 lung cancers, 35 (49%) LAC and 36 (51%)
LSCC. After RNA isolation and reverse transcription, relative RNA expression level
was evaluated using Real Time PCR and TaqMan technology. Ca9 and Ca12 expression
status was calculated according to the 2-ΔΔCT method. We used median value
of expression to designate low and high expression groups. High level of Ca9 and
Ca12 expression were detected in 49% (35/71) and 48% (34/71) of NSCLC samples,
respectively. Low levels of expression were identified in the rest of the specimens.
High expression of Ca12 was associated with LSCC subtype (p<0.0001). No associations
between Ca9 or Ca12 expression and clinicopathological parameters were
detected when assessed independently. However, patients with high expression of
both Ca9 and Ca12 lived significantly shorter compared to the Ca9/Ca12 low expression
group, (p=0.02). Our results suggest that Ca12 expression contributes to
the differences observed between LAC and LSCC tumors. The upregulation of Ca12 may promote the aggressive behavior of NSCLC. Ca9-high/Ca12-high expression
constitutes a ‘high risk’ profile in NSCLC.
AB  - Карцином плућа је најчешће дијагностикована и најсмртоноснија малигна болест у свету. Аденокрацином плућа (енг. lung adenocarcinoma, LAC) и карцином сквамозних ћелија плућа (енг. lung squamous cell carcinoma, LSCC) су два подтипа неситноћелијског карцинома плућа са израженим разликама у кључним клиничким и биолошким карактеристикама. Упркос томе, ови подтипови се најчешће лече на врло сличан начин. Изузетно је важно да се разјасне механизми у основи ових разлика како би се успоставили бољи биомаркери и приступи у лечењу. У бројним типовима тумора примећена је повећана експресија карбонске анхидразе (Са) 9 и 12. Са9 и Са12 имају круцијалну улогу у одржавању неутралне унутарћелијске вредности рН и киселе ванћелијске микросредине што стимулише пролиферцију и метастазирање ћелија тумора. Наши циљеви су били да детектујемо могуће разлике у нивоу експресије Са9 и Са12 у LAC и LSCC, и да истражимо да ли је експресија Са9 и Са12 асоцирана са клиничким током и исходом болести. Испитали смо експресију Са9 и Са12 у 71 узорку карцинома плућа, 35 (49%) LAC и 36 (51%) LSCC. Након изолације РНК и реверзне транскрипције, релативни ниво експресије РНК утврђен је коришћењем квантитативног РСR-а у реалном времену базираног на TaqMan технологији. За израчунавање статуса експресије Са9 и Са12 коришћена је 2-ΔΔCT метода. Употребили смо медијану вредности експресије да дефинишемо групе са високом, односно ниском експресијом. Висок ниво експресије Са9 детектован је у 49% (35/71), а Са12 у 48% (34/71) узорака. Низак ниво експресије је идентификован у преосталим узорцима. Висока експресија Са12 била је асоцирана са LSCC подтипом (р<0.0001). Када су експресија Са9 и Са12 посматране независно, није уочена њихова асоцијација са клиничко-хистопатолошким параметрима. Међутим, пацијенти који су истовремено имали високу експресију и Са9 и Са12 су живели значајно краће у односу на пацијенте са ниском експресијом Са9/Са12, (р=0.02). Наши резултати сугеришу да експресија Са12 доприноси разликама уоченим између LAC и LSCC тумора. Појачана експресија Са12 можда подстиче агресивно понашање неситноћелијског карцинома плућа. Са9 висока/Са12 висока експресија представља профил “високог ризика” у неситноћелијском карциному плућа.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma
T1  - Разлике у експресији карбонске анхидразе 9 и 12 у аденокарциному плућа и карциному сквамозних ћелија плућа
SP  - 78
EP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5771
ER  - 

@conference{
author = "Nedeljković, Milica and Stojišić, Jelena and Tanić, Nasta and Murganić, Blagoje and Tomić, Tijana and Ademović, Nejla and Tanić, Nikola",
year = "2022",
abstract = "Lung cancer is the most frequently diagnosed and lethal malignancy in the
world. Lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC)
are two subtypes of non-small cell lung cancer (NSCLC) which differ markedly in
key clinical and biological features. Despite this, they are usually treated similarly.
It is imperative to elucidate the mechanisms behind these differences in order to
implement better therapeutic modalities and biomarkers. Increased expression of
carbonic anhydrases Ca9 and Ca12 was observed in a broad array of tumors. Ca9
and Ca12 have a crucial role in the maintenance of the neutral intracellular pH and
the acidic extracellular microenvironment which stimulates the proliferation and
metastasis of tumor cells. Our aim was to detect possible difference in expression
level of Ca9 and Ca12 in LAC and LSCC, and to investigate whether the expression
of Ca9 and Ca12 was associated with the clinical course and outcome. We evaluated
the Ca9 and Ca12 expressions in 71 lung cancers, 35 (49%) LAC and 36 (51%)
LSCC. After RNA isolation and reverse transcription, relative RNA expression level
was evaluated using Real Time PCR and TaqMan technology. Ca9 and Ca12 expression
status was calculated according to the 2-ΔΔCT method. We used median value
of expression to designate low and high expression groups. High level of Ca9 and
Ca12 expression were detected in 49% (35/71) and 48% (34/71) of NSCLC samples,
respectively. Low levels of expression were identified in the rest of the specimens.
High expression of Ca12 was associated with LSCC subtype (p<0.0001). No associations
between Ca9 or Ca12 expression and clinicopathological parameters were
detected when assessed independently. However, patients with high expression of
both Ca9 and Ca12 lived significantly shorter compared to the Ca9/Ca12 low expression
group, (p=0.02). Our results suggest that Ca12 expression contributes to
the differences observed between LAC and LSCC tumors. The upregulation of Ca12 may promote the aggressive behavior of NSCLC. Ca9-high/Ca12-high expression
constitutes a ‘high risk’ profile in NSCLC., Карцином плућа је најчешће дијагностикована и најсмртоноснија малигна болест у свету. Аденокрацином плућа (енг. lung adenocarcinoma, LAC) и карцином сквамозних ћелија плућа (енг. lung squamous cell carcinoma, LSCC) су два подтипа неситноћелијског карцинома плућа са израженим разликама у кључним клиничким и биолошким карактеристикама. Упркос томе, ови подтипови се најчешће лече на врло сличан начин. Изузетно је важно да се разјасне механизми у основи ових разлика како би се успоставили бољи биомаркери и приступи у лечењу. У бројним типовима тумора примећена је повећана експресија карбонске анхидразе (Са) 9 и 12. Са9 и Са12 имају круцијалну улогу у одржавању неутралне унутарћелијске вредности рН и киселе ванћелијске микросредине што стимулише пролиферцију и метастазирање ћелија тумора. Наши циљеви су били да детектујемо могуће разлике у нивоу експресије Са9 и Са12 у LAC и LSCC, и да истражимо да ли је експресија Са9 и Са12 асоцирана са клиничким током и исходом болести. Испитали смо експресију Са9 и Са12 у 71 узорку карцинома плућа, 35 (49%) LAC и 36 (51%) LSCC. Након изолације РНК и реверзне транскрипције, релативни ниво експресије РНК утврђен је коришћењем квантитативног РСR-а у реалном времену базираног на TaqMan технологији. За израчунавање статуса експресије Са9 и Са12 коришћена је 2-ΔΔCT метода. Употребили смо медијану вредности експресије да дефинишемо групе са високом, односно ниском експресијом. Висок ниво експресије Са9 детектован је у 49% (35/71), а Са12 у 48% (34/71) узорака. Низак ниво експресије је идентификован у преосталим узорцима. Висока експресија Са12 била је асоцирана са LSCC подтипом (р<0.0001). Када су експресија Са9 и Са12 посматране независно, није уочена њихова асоцијација са клиничко-хистопатолошким параметрима. Међутим, пацијенти који су истовремено имали високу експресију и Са9 и Са12 су живели значајно краће у односу на пацијенте са ниском експресијом Са9/Са12, (р=0.02). Наши резултати сугеришу да експресија Са12 доприноси разликама уоченим између LAC и LSCC тумора. Појачана експресија Са12 можда подстиче агресивно понашање неситноћелијског карцинома плућа. Са9 висока/Са12 висока експресија представља профил “високог ризика” у неситноћелијском карциному плућа.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma, Разлике у експресији карбонске анхидразе 9 и 12 у аденокарциному плућа и карциному сквамозних ћелија плућа",
pages = "78-81",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5771"
}

Nedeljković, M., Stojišić, J., Tanić, N., Murganić, B., Tomić, T., Ademović, N.,& Tanić, N.. (2022). Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 78-81.
https://hdl.handle.net/21.15107/rcub_ibiss_5771

Nedeljković M, Stojišić J, Tanić N, Murganić B, Tomić T, Ademović N, Tanić N. Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:78-81.
https://hdl.handle.net/21.15107/rcub_ibiss_5771 .

Nedeljković, Milica, Stojišić, Jelena, Tanić, Nasta, Murganić, Blagoje, Tomić, Tijana, Ademović, Nejla, Tanić, Nikola, "Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):78-81,
https://hdl.handle.net/21.15107/rcub_ibiss_5771 .

TY  - JOUR
AU  - Tanić, Nikola
AU  - Dramićanin, Tatjana
AU  - Ademović, Nejla
AU  - Tomić, Tijana
AU  - Murganić, Blagoje
AU  - Milovanović, Zorka
AU  - Nedeljković, Milica
AU  - Tanić, Nasta
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5362
AB  - Introduction. Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. BC is exceptionally heterogeneous disease and therefore distinct treatment modalities are necessary to address these differences. The aim of our study was to investigate the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC response to different treatment modalities and their possible cooperation, on post-operative BC samples.
Methods. Patients were classified, based on applied adjuvant therapy, into four distinct groups: those that received hormonal therapy (HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic therapies that exclude HT. Functional inactivation of TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and hypermethylation analysis.
Results. Our results revealed that TP53 gene was altered in 63 out of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower, 54 out of 90 (60%). Simultaneous inactivation was detected in 43 tested samples (48%) with significant association between two analyzed TSGs. Further, we found that TP53 status has significant influence on patients’ therapy response. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association was found between the type of applied therapy and simultaneous alterations of these two TSGs (p = 0.00001). 
Conclusion. Patients with wtTP53 show significantly better therapy response regardless of the type of therapy, compared to carriers of altered TPp53 gene.
AB  - Uvod. Rak dojke (RD) je najčešći tip maligniteta i vodeći uzrok smrti od raka kod žena širom sveta. RD
je izuzetno heterogena bolest i stoga su neophodni različiti modaliteti lečenja da bi se pokrile ove
razlike. Cilj našeg istraživanja je bio da se ispita uticaj inaktivacije TP53 i PTEN tumor supresorskih
gena (TSG) na odgovor RD na različite modalitete lečenja, kao i njihova moguća saradnja u tome, na
postoperativnim uzorcima RD.
Metode. Pacijentkinje su klasifikovane, na osnovu primenjene adjuvantne terapije, u četiri različite
grupe: one koje su primale samo hormonsku terapiju (HT), hormonsku terapiju u kombinaciji sa hemoterapijom (HT/CHT), hormonsku terapiju u kombinaciji sa hemoterapijom i biološkom terapijom
(HT/CHT/H) i druge sistemske terapije koje isključuju HT. Funkcionalna inaktivacija TP53 i PTEN TSG
je proučavana analizom mutacionog statusa, gubitka heterozigotnosti (LOH) i metilacionog statusa.
Rezultati. Naši rezultati su pokazali da je TP53 gen izmenjen kod 63 od 90 pacijenata (70%), dok je
učestalost promena PTEN gena bila nešto niža, 54 od 90 (60%). Simultana inaktivacija je detektovana
u 43 testirana uzorka (48%) sa značajnom povezanošću između dva analizirana TSG-a. Dalje, pokazali
smo da status TP53 ima značajan uticaj na odgovor pacijenata na terapiju. Suprotno ovome, nismo
pokazali značajnu asocijaciju između mutacionog statusa PTEN-a i različitih modaliteta lečenja. Međutim, utvrđena je značajna povezanost između primenjenih terapija i simultanih inaktivacija ova
dva TSG-a (p = 0,00001).
Zaključak. Pacijenti sa wtTP53 pokazuju značajno bolji terapijski odgovor bez obzira na vrstu terapije u poređenju sa nosiocima mutiranog TP53 gena.
PB  - Republika Srpska, Bosna i Hercegovina: Univerzitet u Istočnom Sarajevu - Medicinski fakultet Foča
T2  - Biomedicinska istraživanja
T1  - The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities
T1  - Uticaj tumor supresorskih gena TP53 i PTEN na odgovor na različite načine lečenja raka dojke
IS  - 2
VL  - 13
DO  - 10.5937/BII2202105T
ER  - 

@article{
author = "Tanić, Nikola and Dramićanin, Tatjana and Ademović, Nejla and Tomić, Tijana and Murganić, Blagoje and Milovanović, Zorka and Nedeljković, Milica and Tanić, Nasta",
year = "2022",
abstract = "Introduction. Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. BC is exceptionally heterogeneous disease and therefore distinct treatment modalities are necessary to address these differences. The aim of our study was to investigate the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC response to different treatment modalities and their possible cooperation, on post-operative BC samples.
Methods. Patients were classified, based on applied adjuvant therapy, into four distinct groups: those that received hormonal therapy (HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic therapies that exclude HT. Functional inactivation of TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and hypermethylation analysis.
Results. Our results revealed that TP53 gene was altered in 63 out of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower, 54 out of 90 (60%). Simultaneous inactivation was detected in 43 tested samples (48%) with significant association between two analyzed TSGs. Further, we found that TP53 status has significant influence on patients’ therapy response. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association was found between the type of applied therapy and simultaneous alterations of these two TSGs (p = 0.00001). 
Conclusion. Patients with wtTP53 show significantly better therapy response regardless of the type of therapy, compared to carriers of altered TPp53 gene., Uvod. Rak dojke (RD) je najčešći tip maligniteta i vodeći uzrok smrti od raka kod žena širom sveta. RD
je izuzetno heterogena bolest i stoga su neophodni različiti modaliteti lečenja da bi se pokrile ove
razlike. Cilj našeg istraživanja je bio da se ispita uticaj inaktivacije TP53 i PTEN tumor supresorskih
gena (TSG) na odgovor RD na različite modalitete lečenja, kao i njihova moguća saradnja u tome, na
postoperativnim uzorcima RD.
Metode. Pacijentkinje su klasifikovane, na osnovu primenjene adjuvantne terapije, u četiri različite
grupe: one koje su primale samo hormonsku terapiju (HT), hormonsku terapiju u kombinaciji sa hemoterapijom (HT/CHT), hormonsku terapiju u kombinaciji sa hemoterapijom i biološkom terapijom
(HT/CHT/H) i druge sistemske terapije koje isključuju HT. Funkcionalna inaktivacija TP53 i PTEN TSG
je proučavana analizom mutacionog statusa, gubitka heterozigotnosti (LOH) i metilacionog statusa.
Rezultati. Naši rezultati su pokazali da je TP53 gen izmenjen kod 63 od 90 pacijenata (70%), dok je
učestalost promena PTEN gena bila nešto niža, 54 od 90 (60%). Simultana inaktivacija je detektovana
u 43 testirana uzorka (48%) sa značajnom povezanošću između dva analizirana TSG-a. Dalje, pokazali
smo da status TP53 ima značajan uticaj na odgovor pacijenata na terapiju. Suprotno ovome, nismo
pokazali značajnu asocijaciju između mutacionog statusa PTEN-a i različitih modaliteta lečenja. Međutim, utvrđena je značajna povezanost između primenjenih terapija i simultanih inaktivacija ova
dva TSG-a (p = 0,00001).
Zaključak. Pacijenti sa wtTP53 pokazuju značajno bolji terapijski odgovor bez obzira na vrstu terapije u poređenju sa nosiocima mutiranog TP53 gena.",
publisher = "Republika Srpska, Bosna i Hercegovina: Univerzitet u Istočnom Sarajevu - Medicinski fakultet Foča",
journal = "Biomedicinska istraživanja",
title = "The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities, Uticaj tumor supresorskih gena TP53 i PTEN na odgovor na različite načine lečenja raka dojke",
number = "2",
volume = "13",
doi = "10.5937/BII2202105T"
}

Tanić, N., Dramićanin, T., Ademović, N., Tomić, T., Murganić, B., Milovanović, Z., Nedeljković, M.,& Tanić, N.. (2022). The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities. in Biomedicinska istraživanja
Republika Srpska, Bosna i Hercegovina: Univerzitet u Istočnom Sarajevu - Medicinski fakultet Foča., 13(2).
https://doi.org/10.5937/BII2202105T

Tanić N, Dramićanin T, Ademović N, Tomić T, Murganić B, Milovanović Z, Nedeljković M, Tanić N. The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities. in Biomedicinska istraživanja. 2022;13(2).
doi:10.5937/BII2202105T .

Tanić, Nikola, Dramićanin, Tatjana, Ademović, Nejla, Tomić, Tijana, Murganić, Blagoje, Milovanović, Zorka, Nedeljković, Milica, Tanić, Nasta, "The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities" in Biomedicinska istraživanja, 13, no. 2 (2022),
https://doi.org/10.5937/BII2202105T . .

TY  - CONF
AU  - Dajić-Stevanović, Zora
AU  - Arsenijević, Nebojša
AU  - Kolašinac, Stefan
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Kanjevac, Tatjana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5293
AB  - Secondary metabolites of plants are known as efficient bioactive compounds used in
prophylaxes and treatment of different disorders and diseases. Plants products have a
long history of use in the treatment of cancer. There are very interesting reports from
ethnobotanical studies, including those from the Balkan region, known for high diversity
of medicinal plants, highlighting the use of various plant drugs as anticancer
agents. More than 3000 plant species were listed as possible anticancer agents. In the last
few decades it was shown that some of plant metabolites exhibit potent and promising
therapeutic effects in cancer treatment. Surprisingly, more than 10,000 phytochemicals
have been identified and used in cancer treatment due to their anti-cancer properties.
The most researched are those belonging to alkaloids, flavonoids, lignans, condensed
tannins, terpenoids (components of essential oils), and others. Additionally, bioactive
compounds could synergistically increase the efficiency of anti-cancer drugs and reduce
their toxic effects. Many successful anti-cancer drugs currently in use, or their
analogues, are plant derived and many more are under clinical trials. This review aims
to address the most reported plants used for cancer treatment in relation to their major
bioactive compounds. Furthermore, possible mechanisms of anticancer activity of
selected plant metabolites will be discussed, including apoptotic pathways, inhibition
of Nuclear Factor-κB (NF-κB), modulation of Wnt/beta-catenin signaling, autophagy,
sensitization of multidrug resistant cancer cells, prevention of cancer cell metastasis
and epigenetic regulation. It is well assumed that high antioxidant activity and anti-inflamamtory
effects of herbal drugs are associated with the anticancer activity. In our
study, several well-known and several autochtonous medicinal plants which expressed
the anticancer potential, will be additionally presented.
AB  - Секундарни метаболити биљака се због свог високог биоактивног дејства ко-
ристе у профилакси и лечењу различитих обољења. Биљне компоненте имају дугу
историју коришћења у третману канцера. Постоје многи занимљиви подаци из
етноботаничких студија, укључујући и оне са подручја Балкана, иначе подруч-
ја познатог по високом диверзитету лековитог биља, о употреби различитих
анти-канцерогених биљака. Више од 3000 биљних врста са анти-канцерогеним
потенцијалом је споменуто у светској литератури. Последњих деценија је пока-
зано да биљни метоболити испољавају високе и обећавајуће терапијске ефекте у
третману канцерогених обољења. Чак 10.000 биоактивних биљних компоненти је
идентификовано као потенцијално анти-канцерогених, међу којима су највише
проучавани алкалоиди, флавоноиди, лигнани, кондензовани танини, терпеноиди
(компоненте етарских уља), и други. Многа биоактивна биљна једињења испо-
љавају синергистичка дејства приликом коришћења са стандардним анти-канце-
рогеним терапеутицима, при чему могу умањити и негативне токсичне ефекте
цитостатика. Наш рад има за циљ да представи најчешће коришћене биљне врсте
у третману канцера у вези са хемијским саставом њихових дрога, тј., доминант-
ним биоактивним компонентама. Такође, биће размотрени и потенцијални ан-
тиканцерогени механизми деловања важнијих биљних секундарних метаболита,
као и њихови ефекти на нпр. апоптозу, инхибицију NF-κB фактора, модулацију
Wnt-бета-катенин сигналних путева, аутофагију, као и позитивне утицаје на ре-
зистентност канцерогених ћелија на различите хемијске агенсе и епигенетичке
одговоре. Иначе је познато да су висока антиоксидативна активност и анти-ин-
фламацијски ефекти биљних дрога повезани са њиховим анти-канцерогеним деј-
ством. Неколико оваквих, у свету добро проучених, као и неколико аутохтоних
врста са нашег подручја, ће бити посебно представљено.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - Plant bioactive compounds in cancer treatment: myth or hope?
SP  - 59
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5293
ER  - 

@conference{
author = "Dajić-Stevanović, Zora and Arsenijević, Nebojša and Kolašinac, Stefan and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Tanić, Nikola and Tanić, Nasta and Kanjevac, Tatjana",
year = "2022",
abstract = "Secondary metabolites of plants are known as efficient bioactive compounds used in
prophylaxes and treatment of different disorders and diseases. Plants products have a
long history of use in the treatment of cancer. There are very interesting reports from
ethnobotanical studies, including those from the Balkan region, known for high diversity
of medicinal plants, highlighting the use of various plant drugs as anticancer
agents. More than 3000 plant species were listed as possible anticancer agents. In the last
few decades it was shown that some of plant metabolites exhibit potent and promising
therapeutic effects in cancer treatment. Surprisingly, more than 10,000 phytochemicals
have been identified and used in cancer treatment due to their anti-cancer properties.
The most researched are those belonging to alkaloids, flavonoids, lignans, condensed
tannins, terpenoids (components of essential oils), and others. Additionally, bioactive
compounds could synergistically increase the efficiency of anti-cancer drugs and reduce
their toxic effects. Many successful anti-cancer drugs currently in use, or their
analogues, are plant derived and many more are under clinical trials. This review aims
to address the most reported plants used for cancer treatment in relation to their major
bioactive compounds. Furthermore, possible mechanisms of anticancer activity of
selected plant metabolites will be discussed, including apoptotic pathways, inhibition
of Nuclear Factor-κB (NF-κB), modulation of Wnt/beta-catenin signaling, autophagy,
sensitization of multidrug resistant cancer cells, prevention of cancer cell metastasis
and epigenetic regulation. It is well assumed that high antioxidant activity and anti-inflamamtory
effects of herbal drugs are associated with the anticancer activity. In our
study, several well-known and several autochtonous medicinal plants which expressed
the anticancer potential, will be additionally presented., Секундарни метаболити биљака се због свог високог биоактивног дејства ко-
ристе у профилакси и лечењу различитих обољења. Биљне компоненте имају дугу
историју коришћења у третману канцера. Постоје многи занимљиви подаци из
етноботаничких студија, укључујући и оне са подручја Балкана, иначе подруч-
ја познатог по високом диверзитету лековитог биља, о употреби различитих
анти-канцерогених биљака. Више од 3000 биљних врста са анти-канцерогеним
потенцијалом је споменуто у светској литератури. Последњих деценија је пока-
зано да биљни метоболити испољавају високе и обећавајуће терапијске ефекте у
третману канцерогених обољења. Чак 10.000 биоактивних биљних компоненти је
идентификовано као потенцијално анти-канцерогених, међу којима су највише
проучавани алкалоиди, флавоноиди, лигнани, кондензовани танини, терпеноиди
(компоненте етарских уља), и други. Многа биоактивна биљна једињења испо-
љавају синергистичка дејства приликом коришћења са стандардним анти-канце-
рогеним терапеутицима, при чему могу умањити и негативне токсичне ефекте
цитостатика. Наш рад има за циљ да представи најчешће коришћене биљне врсте
у третману канцера у вези са хемијским саставом њихових дрога, тј., доминант-
ним биоактивним компонентама. Такође, биће размотрени и потенцијални ан-
тиканцерогени механизми деловања важнијих биљних секундарних метаболита,
као и њихови ефекти на нпр. апоптозу, инхибицију NF-κB фактора, модулацију
Wnt-бета-катенин сигналних путева, аутофагију, као и позитивне утицаје на ре-
зистентност канцерогених ћелија на различите хемијске агенсе и епигенетичке
одговоре. Иначе је познато да су висока антиоксидативна активност и анти-ин-
фламацијски ефекти биљних дрога повезани са њиховим анти-канцерогеним деј-
ством. Неколико оваквих, у свету добро проучених, као и неколико аутохтоних
врста са нашег подручја, ће бити посебно представљено.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "Plant bioactive compounds in cancer treatment: myth or hope?",
pages = "59",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5293"
}

Dajić-Stevanović, Z., Arsenijević, N., Kolašinac, S., Maksimović-Ivanić, D., Mijatović, S., Tanić, N., Tanić, N.,& Kanjevac, T.. (2022). Plant bioactive compounds in cancer treatment: myth or hope?. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 59.
https://hdl.handle.net/21.15107/rcub_ibiss_5293

Dajić-Stevanović Z, Arsenijević N, Kolašinac S, Maksimović-Ivanić D, Mijatović S, Tanić N, Tanić N, Kanjevac T. Plant bioactive compounds in cancer treatment: myth or hope?. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:59.
https://hdl.handle.net/21.15107/rcub_ibiss_5293 .

Dajić-Stevanović, Zora, Arsenijević, Nebojša, Kolašinac, Stefan, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Tanić, Nikola, Tanić, Nasta, Kanjevac, Tatjana, "Plant bioactive compounds in cancer treatment: myth or hope?" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):59,
https://hdl.handle.net/21.15107/rcub_ibiss_5293 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Drača, Dijana
AU  - Dajić-Stevanović, Zora
AU  - Jovanović, Ivan
AU  - Tanić, Nikola
AU  - Mijatović, Sanja
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5290
AB  - Alchemilla vulgaris is well known in traditional medicine especially for the treatment
of gynecological problems in women. Several ethnomedicinal studies for the territory
of Balkan reports its well known biological properties against many conditions such
as infertility, dysmenorrhea, cysts, menopausal complaints and endometriosis.
Concidering ethnomedicinal data on female illnesses, the aim of our study was to
determine whether ethanol extract of Alchemilla vulgaris agg. exert antitumor effect
against mouse breast cancer cells in vitro. Treatment with Alchemilla vulgaris agg. extract
decreased viability of mouse breast cancer cells (4T1) in dose-dependent manner after
72 h. The viability decrease was followed by loss of dividing potential after the treatment.
In parallel with this, certain percentage of 4T1 cells was subjected to programmed cell
death ̶ apoptosis. Detected apoptosis was followed with caspase activation while typical
apoptotic morphology of treated cells was observed by fluorescent microscopy. Apart
from inhibited cell division and induced apoptosis, decreased cell viability was due to
triggered autophagy cell death. In parallel, diminished metastatic potential of these
cells was confirmed by abrogated adhesion, invasion, migration and decreased colony
forming potential after the treatment. All mentioned effects can be connected with
enhanced production of ROS and intracellular NO after the treatment with Alchemilla
vulgaris agg. Taken together, the effect of Alchemilla vulgaris agg. against breast cancer
cells makes this plant worthwhile for further evaluation in the field of oncology.
AB  - Alchemilla vulgaris је добро позната у традиционалној медицини, посебно за
лечење гинеколошких тегоба код жена. Неколико етномедицинских студија за
територију Балкана описује благотворна дејства ове биљке против различитих
патолошких стања попут неплодности, дисменореје, циста, тегоба у менопаузи
и ендометриозе. Циљ нашег истраживања био је да се утврдe антитуморска свој-
ства етанолног екстракта Alchemilla vulgaris agg. на ћелијској линији тумора дојке
4Т1 in vitro. Третман екстрактом Alchemilla vulgaris agg. у трајању од 72 сата је
смањио вијабилитет 4Т1 ћелија на дозно-зависан начин. Смањење вијабилно-
сти праћено је губитком пролиферативног потенцијала ћелија. Поред тога, одре-
ђени проценат 4Т1 ћелија подлегао је програмираној ћелијској смрти познатој
као апоптоза. Детектована апоптоза је праћена активацијом каспаза и додатно
потврђена типичном морфологијом нуклеуса коришћењем флуоресцентне ми-
кроскопије. Свеукупној антитуморској активности екстракта Alchemilla vulgaris
agg. доприноси и ћелијска смрт аутофагијом. Паралелно, метастатски потенцијал
ових ћелија је смањен, што је потврђено смањеном адхезијом, инвазијом, мигра-
цијом и потенцијалом ћелија да формирају колоније. Сви поменути ефекти могу
бити у корелацији са повећаном продукцијом реактивних кисеоничних и азот-
них врста детектованом након третмана. У целини, добијени резултати о делова-
њу Alchemilla vulgaris agg. на ћелије рака дојке чине ову биљку вредном пажње за
даљу евалуацију у области експерименталне онкологије.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - Antitumor properites of alchemilla vulgaris agg.
SP  - 129
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5290
ER  - 

@conference{
author = "Jelača, Sanja and Drača, Dijana and Dajić-Stevanović, Zora and Jovanović, Ivan and Tanić, Nikola and Mijatović, Sanja and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Alchemilla vulgaris is well known in traditional medicine especially for the treatment
of gynecological problems in women. Several ethnomedicinal studies for the territory
of Balkan reports its well known biological properties against many conditions such
as infertility, dysmenorrhea, cysts, menopausal complaints and endometriosis.
Concidering ethnomedicinal data on female illnesses, the aim of our study was to
determine whether ethanol extract of Alchemilla vulgaris agg. exert antitumor effect
against mouse breast cancer cells in vitro. Treatment with Alchemilla vulgaris agg. extract
decreased viability of mouse breast cancer cells (4T1) in dose-dependent manner after
72 h. The viability decrease was followed by loss of dividing potential after the treatment.
In parallel with this, certain percentage of 4T1 cells was subjected to programmed cell
death ̶ apoptosis. Detected apoptosis was followed with caspase activation while typical
apoptotic morphology of treated cells was observed by fluorescent microscopy. Apart
from inhibited cell division and induced apoptosis, decreased cell viability was due to
triggered autophagy cell death. In parallel, diminished metastatic potential of these
cells was confirmed by abrogated adhesion, invasion, migration and decreased colony
forming potential after the treatment. All mentioned effects can be connected with
enhanced production of ROS and intracellular NO after the treatment with Alchemilla
vulgaris agg. Taken together, the effect of Alchemilla vulgaris agg. against breast cancer
cells makes this plant worthwhile for further evaluation in the field of oncology., Alchemilla vulgaris је добро позната у традиционалној медицини, посебно за
лечење гинеколошких тегоба код жена. Неколико етномедицинских студија за
територију Балкана описује благотворна дејства ове биљке против различитих
патолошких стања попут неплодности, дисменореје, циста, тегоба у менопаузи
и ендометриозе. Циљ нашег истраживања био је да се утврдe антитуморска свој-
ства етанолног екстракта Alchemilla vulgaris agg. на ћелијској линији тумора дојке
4Т1 in vitro. Третман екстрактом Alchemilla vulgaris agg. у трајању од 72 сата је
смањио вијабилитет 4Т1 ћелија на дозно-зависан начин. Смањење вијабилно-
сти праћено је губитком пролиферативног потенцијала ћелија. Поред тога, одре-
ђени проценат 4Т1 ћелија подлегао је програмираној ћелијској смрти познатој
као апоптоза. Детектована апоптоза је праћена активацијом каспаза и додатно
потврђена типичном морфологијом нуклеуса коришћењем флуоресцентне ми-
кроскопије. Свеукупној антитуморској активности екстракта Alchemilla vulgaris
agg. доприноси и ћелијска смрт аутофагијом. Паралелно, метастатски потенцијал
ових ћелија је смањен, што је потврђено смањеном адхезијом, инвазијом, мигра-
цијом и потенцијалом ћелија да формирају колоније. Сви поменути ефекти могу
бити у корелацији са повећаном продукцијом реактивних кисеоничних и азот-
них врста детектованом након третмана. У целини, добијени резултати о делова-
њу Alchemilla vulgaris agg. на ћелије рака дојке чине ову биљку вредном пажње за
даљу евалуацију у области експерименталне онкологије.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "Antitumor properites of alchemilla vulgaris agg.",
pages = "129",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5290"
}

Jelača, S., Drača, D., Dajić-Stevanović, Z., Jovanović, I., Tanić, N., Mijatović, S., Arsenijević, N.,& Maksimović-Ivanić, D.. (2022). Antitumor properites of alchemilla vulgaris agg.. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 129.
https://hdl.handle.net/21.15107/rcub_ibiss_5290

Jelača S, Drača D, Dajić-Stevanović Z, Jovanović I, Tanić N, Mijatović S, Arsenijević N, Maksimović-Ivanić D. Antitumor properites of alchemilla vulgaris agg.. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:129.
https://hdl.handle.net/21.15107/rcub_ibiss_5290 .

Jelača, Sanja, Drača, Dijana, Dajić-Stevanović, Zora, Jovanović, Ivan, Tanić, Nikola, Mijatović, Sanja, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Antitumor properites of alchemilla vulgaris agg." in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):129,
https://hdl.handle.net/21.15107/rcub_ibiss_5290 .

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 . .

TY  - CONF
AU  - Jelača, Sanja
AU  - Dajić-Stevanović, Zora
AU  - Vuković, Nenad
AU  - Trifunović, Srećko
AU  - Drača, Dijana
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Tanić, Nasta
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5591
AB  - U okviru projekta bilateralne saradnje Republike Srbije i Narodne Republike Kine testirana su antitumorska svojstva ukupnih ekstrakata izolovanih iz biljaka: rtanjski čaj (Satureja montana subsp. kitaibelii), trava iva (Teucrium montanum), virak (Alchemilla vulgaris agg.), bela imela (Viscum album subsp. album), zečiji trn (Ononis spinosa), detelina kamenjarka (Anthyllis vulneraria), čestoslavica (Veronica chamaedrys), različak (Centaurea cyanis), svećica (Gentiana asclepiadea), vilino sito (Carlina acaulis), mirisni zdravac (Geranium macrorrhyzum), kotrljan (Eryngium amethystinum), izop (Hyssopus officinalis) i slatinski pelin (Artemisia santonicum). Efekat ekstrakata ispitivan je na humanim ćelijskim linijama tumora dojke MCF-7, melanoma A375, karcinoma pluća A549 i kolona HCT116, kao i ćelijama peritonealnog eksudata miša. Uticaj na vijabilnost tumorskih ćelija praćen je sulforodamin (SRB) i testom mitohondrijalne dehidrogenaze (MTT). Ekstrakti biljaka svećice, različka, vilinog sita i izopa nisu redukovali vijabilitet tumorskih ćelija. Sa druge strane ekstrakti ive, virka, mirisnog zdravca i kotrljana su pokazali značajan potencijal da ograniče rast ćelijske linije karcinoma pluća inhibirajući deobu ćelija i indukujući kaspazama posredovanu apoptozu. Tumoricidna aktivnost ekstrakata deteline kamenjarke i rtanjskog čaja je bila najsnažnija na liniji kancera dojke dok je pad vijabilnosti najverovatnije posledica intenzivirane autofagije i smanjenog proliferativnog kapaciteta ćelija. Tretmani ćelija ispitivanim ekstraktima bili su praćeni smanjenjem produkcije slobodnih radikala kiseonika/ azota ukazujući na to da ekstrakti poseduju izvestan antioksidativni potencijal ali da ove reaktivne vrste nisu medijatori njihove tumoricidne aktivnosti. Testirani ekstrakti koji su ispoljili antitumorsku aktivnost, sa izuzetkom ekstrakta kotrljana, su bili u istom opsegu doza netoksični za ćelije peritonealnog eksudata zdravih miševa ukazujući na selektivnost prema malignom fenotipu.
PB  - Kragujevac: Fakultet medicinskih nauka Univerziteta
C3  - Knjiga sažetaka: Simpozijum Efekti aktivnih supstanci u eksperimentalnim in vitro i in vivo modelima; 2019 Dec 26; Kragujevac, Serbia
T1  - Antitumorska svojstva ekstrakata biljaka sa teritorije Balkana
T1  - Антитуморска својства eкстраката биљака са територије Балкана
SP  - 16
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5591
ER  - 

@conference{
author = "Jelača, Sanja and Dajić-Stevanović, Zora and Vuković, Nenad and Trifunović, Srećko and Drača, Dijana and Tanić, Nikola and Arsenijević, Nebojša and Tanić, Nasta and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "U okviru projekta bilateralne saradnje Republike Srbije i Narodne Republike Kine testirana su antitumorska svojstva ukupnih ekstrakata izolovanih iz biljaka: rtanjski čaj (Satureja montana subsp. kitaibelii), trava iva (Teucrium montanum), virak (Alchemilla vulgaris agg.), bela imela (Viscum album subsp. album), zečiji trn (Ononis spinosa), detelina kamenjarka (Anthyllis vulneraria), čestoslavica (Veronica chamaedrys), različak (Centaurea cyanis), svećica (Gentiana asclepiadea), vilino sito (Carlina acaulis), mirisni zdravac (Geranium macrorrhyzum), kotrljan (Eryngium amethystinum), izop (Hyssopus officinalis) i slatinski pelin (Artemisia santonicum). Efekat ekstrakata ispitivan je na humanim ćelijskim linijama tumora dojke MCF-7, melanoma A375, karcinoma pluća A549 i kolona HCT116, kao i ćelijama peritonealnog eksudata miša. Uticaj na vijabilnost tumorskih ćelija praćen je sulforodamin (SRB) i testom mitohondrijalne dehidrogenaze (MTT). Ekstrakti biljaka svećice, različka, vilinog sita i izopa nisu redukovali vijabilitet tumorskih ćelija. Sa druge strane ekstrakti ive, virka, mirisnog zdravca i kotrljana su pokazali značajan potencijal da ograniče rast ćelijske linije karcinoma pluća inhibirajući deobu ćelija i indukujući kaspazama posredovanu apoptozu. Tumoricidna aktivnost ekstrakata deteline kamenjarke i rtanjskog čaja je bila najsnažnija na liniji kancera dojke dok je pad vijabilnosti najverovatnije posledica intenzivirane autofagije i smanjenog proliferativnog kapaciteta ćelija. Tretmani ćelija ispitivanim ekstraktima bili su praćeni smanjenjem produkcije slobodnih radikala kiseonika/ azota ukazujući na to da ekstrakti poseduju izvestan antioksidativni potencijal ali da ove reaktivne vrste nisu medijatori njihove tumoricidne aktivnosti. Testirani ekstrakti koji su ispoljili antitumorsku aktivnost, sa izuzetkom ekstrakta kotrljana, su bili u istom opsegu doza netoksični za ćelije peritonealnog eksudata zdravih miševa ukazujući na selektivnost prema malignom fenotipu.",
publisher = "Kragujevac: Fakultet medicinskih nauka Univerziteta",
journal = "Knjiga sažetaka: Simpozijum Efekti aktivnih supstanci u eksperimentalnim in vitro i in vivo modelima; 2019 Dec 26; Kragujevac, Serbia",
title = "Antitumorska svojstva ekstrakata biljaka sa teritorije Balkana, Антитуморска својства eкстраката биљака са територије Балкана",
pages = "16",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5591"
}

Jelača, S., Dajić-Stevanović, Z., Vuković, N., Trifunović, S., Drača, D., Tanić, N., Arsenijević, N., Tanić, N., Mijatović, S.,& Maksimović-Ivanić, D.. (2019). Antitumorska svojstva ekstrakata biljaka sa teritorije Balkana. in Knjiga sažetaka: Simpozijum Efekti aktivnih supstanci u eksperimentalnim in vitro i in vivo modelima; 2019 Dec 26; Kragujevac, Serbia
Kragujevac: Fakultet medicinskih nauka Univerziteta., 16.
https://hdl.handle.net/21.15107/rcub_ibiss_5591

Jelača S, Dajić-Stevanović Z, Vuković N, Trifunović S, Drača D, Tanić N, Arsenijević N, Tanić N, Mijatović S, Maksimović-Ivanić D. Antitumorska svojstva ekstrakata biljaka sa teritorije Balkana. in Knjiga sažetaka: Simpozijum Efekti aktivnih supstanci u eksperimentalnim in vitro i in vivo modelima; 2019 Dec 26; Kragujevac, Serbia. 2019;:16.
https://hdl.handle.net/21.15107/rcub_ibiss_5591 .

Jelača, Sanja, Dajić-Stevanović, Zora, Vuković, Nenad, Trifunović, Srećko, Drača, Dijana, Tanić, Nikola, Arsenijević, Nebojša, Tanić, Nasta, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Antitumorska svojstva ekstrakata biljaka sa teritorije Balkana" in Knjiga sažetaka: Simpozijum Efekti aktivnih supstanci u eksperimentalnim in vitro i in vivo modelima; 2019 Dec 26; Kragujevac, Serbia (2019):16,
https://hdl.handle.net/21.15107/rcub_ibiss_5591 .

TY  - JOUR
AU  - Dragoj, Miodrag
AU  - Banković, Jasna
AU  - Podolski-Renić, Ana
AU  - Stojković Burić, Sonja
AU  - Pešić, Milica
AU  - Tanić, Nikola
AU  - Stanković, Tijana
PY  - 2019
UR  - https://content.sciendo.com/view/journals/jomb/ahead-of-print/article-10.2478-jomb-2018-0022.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3099
AB  - Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACTR3 and E2F4. Methods: We analyzed MYC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. MYC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Results: MYC expression was significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed MYC and altered PHACTR3 or E2F4 showed trend of shorter survival. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.
T2  - Journal of Medical Biochemistry
T1  - Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis
VL  - 37
DO  - 10.2478/jomb-2018-0022
SP  - 188
EP  - 195
ER  - 

@article{
author = "Dragoj, Miodrag and Banković, Jasna and Podolski-Renić, Ana and Stojković Burić, Sonja and Pešić, Milica and Tanić, Nikola and Stanković, Tijana",
year = "2019",
abstract = "Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACTR3 and E2F4. Methods: We analyzed MYC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. MYC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Results: MYC expression was significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed MYC and altered PHACTR3 or E2F4 showed trend of shorter survival. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.",
journal = "Journal of Medical Biochemistry",
title = "Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis",
volume = "37",
doi = "10.2478/jomb-2018-0022",
pages = "188-195"
}

Dragoj, M., Banković, J., Podolski-Renić, A., Stojković Burić, S., Pešić, M., Tanić, N.,& Stanković, T.. (2019). Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis. in Journal of Medical Biochemistry, 37, 188-195.
https://doi.org/10.2478/jomb-2018-0022

Dragoj M, Banković J, Podolski-Renić A, Stojković Burić S, Pešić M, Tanić N, Stanković T. Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis. in Journal of Medical Biochemistry. 2019;37:188-195.
doi:10.2478/jomb-2018-0022 .

Dragoj, Miodrag, Banković, Jasna, Podolski-Renić, Ana, Stojković Burić, Sonja, Pešić, Milica, Tanić, Nikola, Stanković, Tijana, "Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis" in Journal of Medical Biochemistry, 37 (2019):188-195,
https://doi.org/10.2478/jomb-2018-0022 . .

TY  - JOUR
AU  - Milošević, Zorica
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Tsimplouli, Chrisiida
AU  - Sereti, Evangelia
AU  - Dragoj, Miodrag
AU  - Paunović, Verica
AU  - Milovanović, Zorka
AU  - Nešović, Marija
AU  - Tanić, Nikola
AU  - Dimas, Kostantinos
AU  - Pešić, Milica
PY  - 2018
UR  - https://link.springer.com/article/10.1007%2Fs13402-018-0380-x
UR  - https://radar.ibiss.bg.ac.rs/123456789/3887
AB  - Purpose: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate.
Methods: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies.
Results: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth.
Conclusions: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.
PB  - Basel : Springer Nature
T2  - Cellular Oncology (Dordrecht)
T1  - Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma
VL  - 41
DO  - 10.1007/s13402-018-0380-x
SP  - 409
EP  - 426
ER  - 

@article{
author = "Milošević, Zorica and Banković, Jasna and Dinić, Jelena and Tsimplouli, Chrisiida and Sereti, Evangelia and Dragoj, Miodrag and Paunović, Verica and Milovanović, Zorka and Nešović, Marija and Tanić, Nikola and Dimas, Kostantinos and Pešić, Milica",
year = "2018",
abstract = "Purpose: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate.
Methods: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies.
Results: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth.
Conclusions: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.",
publisher = "Basel : Springer Nature",
journal = "Cellular Oncology (Dordrecht)",
title = "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma",
volume = "41",
doi = "10.1007/s13402-018-0380-x",
pages = "409-426"
}

Milošević, Z., Banković, J., Dinić, J., Tsimplouli, C., Sereti, E., Dragoj, M., Paunović, V., Milovanović, Z., Nešović, M., Tanić, N., Dimas, K.,& Pešić, M.. (2018). Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma. in Cellular Oncology (Dordrecht)
Basel : Springer Nature., 41, 409-426.
https://doi.org/10.1007/s13402-018-0380-x

Milošević Z, Banković J, Dinić J, Tsimplouli C, Sereti E, Dragoj M, Paunović V, Milovanović Z, Nešović M, Tanić N, Dimas K, Pešić M. Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma. in Cellular Oncology (Dordrecht). 2018;41:409-426.
doi:10.1007/s13402-018-0380-x .

Milošević, Zorica, Banković, Jasna, Dinić, Jelena, Tsimplouli, Chrisiida, Sereti, Evangelia, Dragoj, Miodrag, Paunović, Verica, Milovanović, Zorka, Nešović, Marija, Tanić, Nikola, Dimas, Kostantinos, Pešić, Milica, "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma" in Cellular Oncology (Dordrecht), 41 (2018):409-426,
https://doi.org/10.1007/s13402-018-0380-x . .

TY  - JOUR
AU  - Milošević, Zorica
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Tsimplouli, Chrisiida
AU  - Sereti, Evangelia
AU  - Dragoj, Miodrag
AU  - Paunović, Verica
AU  - Milovanović, Zorka
AU  - Stepanović, Marija
AU  - Tanić, Nikola
AU  - Dimas, Kostantinos
AU  - Pešić, Milica
PY  - 2018
UR  - http://link.springer.com/10.1007/s13402-018-0380-x
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3128
AB  - PURPOSE Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. METHODS Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. RESULTS Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. CONCLUSIONS Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.
T2  - Cellular Oncology (Dordrecht)
T1  - Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.
IS  - 4
VL  - 41
DO  - 10.1007/s13402-018-0380-x
SP  - 409
EP  - 426
ER  - 

@article{
author = "Milošević, Zorica and Banković, Jasna and Dinić, Jelena and Tsimplouli, Chrisiida and Sereti, Evangelia and Dragoj, Miodrag and Paunović, Verica and Milovanović, Zorka and Stepanović, Marija and Tanić, Nikola and Dimas, Kostantinos and Pešić, Milica",
year = "2018",
abstract = "PURPOSE Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. METHODS Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. RESULTS Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. CONCLUSIONS Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.",
journal = "Cellular Oncology (Dordrecht)",
title = "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.",
number = "4",
volume = "41",
doi = "10.1007/s13402-018-0380-x",
pages = "409-426"
}

Milošević, Z., Banković, J., Dinić, J., Tsimplouli, C., Sereti, E., Dragoj, M., Paunović, V., Milovanović, Z., Stepanović, M., Tanić, N., Dimas, K.,& Pešić, M.. (2018). Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.. in Cellular Oncology (Dordrecht), 41(4), 409-426.
https://doi.org/10.1007/s13402-018-0380-x

Milošević Z, Banković J, Dinić J, Tsimplouli C, Sereti E, Dragoj M, Paunović V, Milovanović Z, Stepanović M, Tanić N, Dimas K, Pešić M. Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.. in Cellular Oncology (Dordrecht). 2018;41(4):409-426.
doi:10.1007/s13402-018-0380-x .

Milošević, Zorica, Banković, Jasna, Dinić, Jelena, Tsimplouli, Chrisiida, Sereti, Evangelia, Dragoj, Miodrag, Paunović, Verica, Milovanović, Zorka, Stepanović, Marija, Tanić, Nikola, Dimas, Kostantinos, Pešić, Milica, "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma." in Cellular Oncology (Dordrecht), 41, no. 4 (2018):409-426,
https://doi.org/10.1007/s13402-018-0380-x . .

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 . .