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  - Jovanović, Irena
AU  - Nedeljković, Milica
AU  - Medić-Milijić, Nataša
AU  - Spurnić, Igor
AU  - Milovanović, Zorka
AU  - Tomić, Tijana
AU  - Tanić, Nasta
AU  - Tanić, Nikola
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6324
AB  - Background: 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 of cludin 3, claudin 4 and claudin 7 in TNBC promotion and progression. Claudins are tight junction (TJ) integral membrane proteins that are key regulators of the paracellular pathway. Materials and methods: 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 from 2009 to 2014. The expression of claudin 3, 4 and 7 was observed using the immunohistochemical staining method. The Allred scoring system was used with cut-off values: ≤4 and >4 (low/high expression). Results: Our results showed that the expression of claudins 3 and 4 correlate with higher nuclear gradus and low desease free interval (DFI). More over, the expression of claudin 3 and claudin 4 correlates (Spearman test p˂0.0001). In addition, high expression of claudin 7 is signifi cantly related to low DFI of patients (p˂0.005) and distant metastases. Conclusions: We concluded that claudin 3, claudin 4 and claudin 7 have significant impact on TNBC progression. Namely, elevated expression of these proteins significantly correlates with low DFI and distant metastases. In other words, elevated expression of claudins is a bad news for TNBC patients. Therefore, the expression of claudins could be a good prognostic marker for TNBC patients and potential target for future therapy protocols.
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  - Role of claudins 3,4 and 7 in triple negative breast cancer progression
SP  - 63
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6324
ER  - 

@conference{
author = "Jovanović, Irena and Nedeljković, Milica and Medić-Milijić, Nataša and Spurnić, Igor and Milovanović, Zorka and Tomić, Tijana and Tanić, Nasta and Tanić, Nikola",
year = "2023",
abstract = "Background: 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 of cludin 3, claudin 4 and claudin 7 in TNBC promotion and progression. Claudins are tight junction (TJ) integral membrane proteins that are key regulators of the paracellular pathway. Materials and methods: 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 from 2009 to 2014. The expression of claudin 3, 4 and 7 was observed using the immunohistochemical staining method. The Allred scoring system was used with cut-off values: ≤4 and >4 (low/high expression). Results: Our results showed that the expression of claudins 3 and 4 correlate with higher nuclear gradus and low desease free interval (DFI). More over, the expression of claudin 3 and claudin 4 correlates (Spearman test p˂0.0001). In addition, high expression of claudin 7 is signifi cantly related to low DFI of patients (p˂0.005) and distant metastases. Conclusions: We concluded that claudin 3, claudin 4 and claudin 7 have significant impact on TNBC progression. Namely, elevated expression of these proteins significantly correlates with low DFI and distant metastases. In other words, elevated expression of claudins is a bad news for TNBC patients. Therefore, the expression of claudins could be a good prognostic marker for TNBC patients and potential target for future therapy protocols.",
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 = "Role of claudins 3,4 and 7 in triple negative breast cancer progression",
pages = "63",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6324"
}

Jovanović, I., Nedeljković, M., Medić-Milijić, N., Spurnić, I., Milovanović, Z., Tomić, T., Tanić, N.,& Tanić, N.. (2023). Role of claudins 3,4 and 7 in triple negative breast cancer progression. 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., 63.
https://hdl.handle.net/21.15107/rcub_ibiss_6324

Jovanović I, Nedeljković M, Medić-Milijić N, Spurnić I, Milovanović Z, Tomić T, Tanić N, Tanić N. Role of claudins 3,4 and 7 in triple negative breast cancer progression. 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;:63.
https://hdl.handle.net/21.15107/rcub_ibiss_6324 .

Jovanović, Irena, Nedeljković, Milica, Medić-Milijić, Nataša, Spurnić, Igor, Milovanović, Zorka, Tomić, Tijana, Tanić, Nasta, Tanić, Nikola, "Role of claudins 3,4 and 7 in triple negative breast cancer progression" 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):63,
https://hdl.handle.net/21.15107/rcub_ibiss_6324 .

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  - 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  - 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  - 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  - 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  - 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  - Ristić, Nataša
AU  - Ajdžanović, Vladimir
AU  - Trifunović, Svetlana
AU  - Tanić, Nasta
AU  - Bujišić, Nada
AU  - Milošević, Verica
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6056
AB  - Th e eff ects of estradiol-dipropionate (EDP) or human chorionic gonadotropin (hCG) on immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats were investigated. Th e fi rst group of females received fi ve injections of EDP (0.25 mg/kg b.w.) during the neonatal period of life, and was further divided into two subgroups which were sacrifi ced at the infantile period (17th day) or at the peripubertal period (38th day). Th e second group received two doses of hCG (50 IU/kg b.w.) on the 15th and 16th day of life in the fi rst subgroup, and on the 36th and 37th days of life in the second subgroup, while they were sacrifi ced 24 h after the last treatment, respectively. Th e control females were injected with an equivalent volume of the vehicle and sacrifi ced according to the appropriate schedules as the hormone treated rats. EDP treatment decreased GH cell volume density in infant and peripubertal females, by 38% and 76% (p<0.05) respectively, in comparison with the controls. Th e number of GH cells per mm2 in infantile and peripubertal period was decreased in EDP treated animals by 26% and 53% (p<0.05) respectively, compared to the controls. Also, upon EDP treatment in both periods, GH cells were diminished in size and less intensely immunolabelled than in the control groups. Th e morphometric parameters in animals treated with hCG were insignifi cantly changed in both analyzed periods, in comparison with the controls. Unlike hCG, EDP manifested clear inhibitory eff ects on the immunohistomorphometric characteristics of GH cells in examined female rats.
AB  - U studiji su ispitivani efekti estradiol dipropionata (EDP) i humanog horionskog gonadotropina na imunohistomorfometrijske karakteristike hipofi znih GH ćelija veoma mladih i peripubertalnih ženki pacova. Prva grupa ženki je tokom neonatalnog perioda života primila pet injekcija EDP-a (0.25 mg/kg b.w.), a naknadno je podeljena na dve podgrupe koje su žrtvovane kao veoma mlade (17. dan) ili u peripubertalnom periodu (38. dan). Druga grupa je primila dve doze hCG-a (50 IU/kg b.w.) 15. i 16. dana života (prva podgrupa), odnosno 36. i 37. dana života (druga podgrupa), a žrtvovane su 24h nakon poslednjeg tratmana, ponaosob. Kontrolne ženke pacova su primile ekvivalentan volumen rastvarača i žrtvovane su po obrascu koji je važio za hormonima tretirane grupe. Tretman EDP-om je prouzrokovao smanjenje volumenske gustine GH ćelija kod veoma mladih i peripubertalnih ženki pacova za 38% odnosno 76% (p<0.05) u poređenju sa kontrolama. Broj GH ćelija po mm2kod veoma mladih i peripubertanih životinja je smanjen nakon EDP tretmana za 26% odnosno 53% (p<0.05) poredeći sa kontrolnim vrednostima. Takođe, tretman EDP-om u oba perioda je izazvao smanjenje dimenzija i intenziteta imunobojenja GH ćelija u odnosu na kontrole. Morfometrijski parametri kod životinja tretiranih hCG-om u oba perioda nisu značajno promenjeni u poređenju sa kontrolnim vrednostima. Za razliku od hCG-a, EDP je ispoljio jasne inhibitorne efekte na imunohistomoprfometrijske karakteristike GH ćelija kod ispitivanih ženki pacova.
PB  - University of Kragujevac, Faculty of Science
T2  - Serbian Journal of Experimental and Clinical Research
T1  - Immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats after treatment with estradiol of human chorionic gonadotropin
IS  - 4
VL  - 16
DO  - 10.1515/SJECR-2015-058
SP  - 281
EP  - 285
ER  - 

@article{
author = "Ristić, Nataša and Ajdžanović, Vladimir and Trifunović, Svetlana and Tanić, Nasta and Bujišić, Nada and Milošević, Verica",
year = "2015",
abstract = "Th e eff ects of estradiol-dipropionate (EDP) or human chorionic gonadotropin (hCG) on immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats were investigated. Th e fi rst group of females received fi ve injections of EDP (0.25 mg/kg b.w.) during the neonatal period of life, and was further divided into two subgroups which were sacrifi ced at the infantile period (17th day) or at the peripubertal period (38th day). Th e second group received two doses of hCG (50 IU/kg b.w.) on the 15th and 16th day of life in the fi rst subgroup, and on the 36th and 37th days of life in the second subgroup, while they were sacrifi ced 24 h after the last treatment, respectively. Th e control females were injected with an equivalent volume of the vehicle and sacrifi ced according to the appropriate schedules as the hormone treated rats. EDP treatment decreased GH cell volume density in infant and peripubertal females, by 38% and 76% (p<0.05) respectively, in comparison with the controls. Th e number of GH cells per mm2 in infantile and peripubertal period was decreased in EDP treated animals by 26% and 53% (p<0.05) respectively, compared to the controls. Also, upon EDP treatment in both periods, GH cells were diminished in size and less intensely immunolabelled than in the control groups. Th e morphometric parameters in animals treated with hCG were insignifi cantly changed in both analyzed periods, in comparison with the controls. Unlike hCG, EDP manifested clear inhibitory eff ects on the immunohistomorphometric characteristics of GH cells in examined female rats., U studiji su ispitivani efekti estradiol dipropionata (EDP) i humanog horionskog gonadotropina na imunohistomorfometrijske karakteristike hipofi znih GH ćelija veoma mladih i peripubertalnih ženki pacova. Prva grupa ženki je tokom neonatalnog perioda života primila pet injekcija EDP-a (0.25 mg/kg b.w.), a naknadno je podeljena na dve podgrupe koje su žrtvovane kao veoma mlade (17. dan) ili u peripubertalnom periodu (38. dan). Druga grupa je primila dve doze hCG-a (50 IU/kg b.w.) 15. i 16. dana života (prva podgrupa), odnosno 36. i 37. dana života (druga podgrupa), a žrtvovane su 24h nakon poslednjeg tratmana, ponaosob. Kontrolne ženke pacova su primile ekvivalentan volumen rastvarača i žrtvovane su po obrascu koji je važio za hormonima tretirane grupe. Tretman EDP-om je prouzrokovao smanjenje volumenske gustine GH ćelija kod veoma mladih i peripubertalnih ženki pacova za 38% odnosno 76% (p<0.05) u poređenju sa kontrolama. Broj GH ćelija po mm2kod veoma mladih i peripubertanih životinja je smanjen nakon EDP tretmana za 26% odnosno 53% (p<0.05) poredeći sa kontrolnim vrednostima. Takođe, tretman EDP-om u oba perioda je izazvao smanjenje dimenzija i intenziteta imunobojenja GH ćelija u odnosu na kontrole. Morfometrijski parametri kod životinja tretiranih hCG-om u oba perioda nisu značajno promenjeni u poređenju sa kontrolnim vrednostima. Za razliku od hCG-a, EDP je ispoljio jasne inhibitorne efekte na imunohistomoprfometrijske karakteristike GH ćelija kod ispitivanih ženki pacova.",
publisher = "University of Kragujevac, Faculty of Science",
journal = "Serbian Journal of Experimental and Clinical Research",
title = "Immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats after treatment with estradiol of human chorionic gonadotropin",
number = "4",
volume = "16",
doi = "10.1515/SJECR-2015-058",
pages = "281-285"
}

Ristić, N., Ajdžanović, V., Trifunović, S., Tanić, N., Bujišić, N.,& Milošević, V.. (2015). Immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats after treatment with estradiol of human chorionic gonadotropin. in Serbian Journal of Experimental and Clinical Research
University of Kragujevac, Faculty of Science., 16(4), 281-285.
https://doi.org/10.1515/SJECR-2015-058

Ristić N, Ajdžanović V, Trifunović S, Tanić N, Bujišić N, Milošević V. Immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats after treatment with estradiol of human chorionic gonadotropin. in Serbian Journal of Experimental and Clinical Research. 2015;16(4):281-285.
doi:10.1515/SJECR-2015-058 .

Ristić, Nataša, Ajdžanović, Vladimir, Trifunović, Svetlana, Tanić, Nasta, Bujišić, Nada, Milošević, Verica, "Immunohistomorphometric characteristics of pituitary GH cells in infant and peripubertal female rats after treatment with estradiol of human chorionic gonadotropin" in Serbian Journal of Experimental and Clinical Research, 16, no. 4 (2015):281-285,
https://doi.org/10.1515/SJECR-2015-058 . .