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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Prvanović, Mirjana
AU  - Nedeljković, Milica
AU  - Tanić, Nasta
AU  - Tomić, Tijana
AU  - Terzić, Tanja
AU  - Milovanović, Zorka
AU  - Maksimović, Zlatko
AU  - Tanić, Nikola
PY  - 2021
UR  - https://www.mdpi.com/2075-1729/11/11/1247
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8621563
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4698
AB  - Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/mTOR protein expression may be more useful in predicting TNBC clinical course than the analysis of single protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a 'high risk' profile of TNBC.
PB  - Basel: MDPI
T2  - Life (Basel, Switzerland)
T1  - Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.
IS  - 11
VL  - 11
DO  - 10.3390/life11111247
SP  - 1247
ER  - 

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

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

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

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

TY  - JOUR
AU  - Nedeljković, Milica
AU  - Tanić, Nasta
AU  - Prvanović, Mirjana
AU  - Milovanović, Zorka
AU  - Tanić, Nikola
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4233
AB  - Background: ATP-binding cassette (ABC) transporters are responsible for the efflux of a wide variety of anti-cancer agents and have been implicated in the chemoresistance of various solid tumors. Chemoresistance is a major cause of therapeutic failure, especially in the highly aggressive triple-negative breast cancer (TNBC) in which, unlike estrogen receptor-expressing (ER+) BC, both endocrine and targeted treatments are ineffectual. We aimed to investigate the level and frequency of expression of the three most important ABC transporter, ABCG2, ABCC1, and ABCB1, according to breast cancer subtype. Methods: We evaluated ABCG2, ABCC1, and ABCB1 protein expressions in 124 primary breast tumors (78 samples were classified as TNBC, while 46 were classified as ER+) by immunohistochemistry and correlated it to clinicopathological characteristics and outcome. Results: All three transporters had significantly higher expression and were more frequently expressed in TNBC compared to ER+ tumors (p < 0.0001). ABCG2 and ABCC1 had a very high level of expression in TNBC that was significantly greater compared to ABCB1 (p < 0.0001). ABCB1 expression was associated with TNBC metastatic spread (p = 0.03). In contrast, TNBC patients with high ABCG2 expression level had significantly longer disease-free interval (p = 0.03) and overall survival (p = 0.007). Conclusion: ABCG2, ABCC1, and ABCB1 expression in breast cancer is subtype-specific and associated with triple-negative tumors. The expression of ABCB1 may be useful as a marker of metastatic spread. Moreover, unexpectedly, our results showed a beneficial effect of ABCG2 expression on TNBC clinical behavior. These findings could have implications for the implementation of future TNBC treatment strategies.
PB  - Springer Japan
T2  - Breast Cancer
T1  - Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer
IS  - 3
VL  - 28
DO  - 10.1007/s12282-020-01210-z
SP  - 727
EP  - 736
ER  - 

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

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

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

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

TY  - JOUR
AU  - Nedeljković, Milica
AU  - Tanić, Nikola
AU  - Dramićanin, Tatjana
AU  - Milovanović, Zorka
AU  - Šušnjar, Snežana
AU  - Milinković, Vedrana
AU  - Vujović, Ivana
AU  - Tanić, Nasta
PY  - 2018
UR  - http://content.sciendo.com/view/journals/jomb/ahead-of-print/article-10.1515-jomb-2018-0012.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3062
AB  - Background: Triple negative breast cancer (TNBC) is characterized by aggressive clinical course and is unresponsive to anti-HER2 and endocrine therapy. TNBC is difficult to treat and is often lethal. Given the need to find new targets for therapy we explored clinicopathological significance of copy number gain of FGFR1 and c-MYC. Our aim was to determine the impact of FGFR1 and c-MYC copy number gain on clinical course and outcome of TNBC. Methods: FGFR1 and c-MYC gene copy number alterations were evaluated in 78 archive TNBC samples using TaqMan based quantitative real time PCR assays. Results: 50% of samples had increased c-MYC copy number. c-MYC copy number gain was associated with TNBC in contrast to ER positive cancers. Our results showed significant correlation between c-MYC copy number gain and high grade of TNBCs. This suggests that c-MYC copy number could be an useful prognostic marker for TNBC patients. c-MYC copy number gain was associated with high pTNM stage as well as lobular and medullary tumor subtypes. 43% of samples had increased FGFR1 copy number. No correlations between FGFR1 copy number gain and clinicopathological variables were observed. Conclusions: We identified c-MYC copy number gain as a prognostic marker for TNBC. Our results indicate that c- MYC may contribute to TNBC progression. We observed no significant association between c-MYC and/or FGFR1 copy number status and patient survival.
T2  - Journal of Medical Biochemistry
T1  - Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer
DO  - 10.1515/jomb-2018-0012
ER  - 

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

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

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

Nedeljković, Milica, Tanić, Nikola, Dramićanin, Tatjana, Milovanović, Zorka, Šušnjar, Snežana, Milinković, Vedrana, Vujović, Ivana, Tanić, Nasta, "Importance of Copy Number Alterations of FGFR1 and C-MYC Genes in Triple Negative Breast Cancer" in Journal of Medical Biochemistry (2018),
https://doi.org/10.1515/jomb-2018-0012 . .

TY  - JOUR
AU  - Miler, Marko
AU  - Jarić, Ivana
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Tanić, Nasta
AU  - Milošević, Verica
AU  - Šošić-Jurjević, Branka 
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0065128116303622
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28262328
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2605
AB  - Citrus flavanones naringenin (NAR) and hesperetin (HES) are potent antioxidants that may contribute to maintenance of health at old age by improving cardiovascular and metabolic status. However, they may also affect thyroid hormone economy. Keeping in mind impaired thyroid function at older age, in this study we tested wheather NAR or HES administration potentiate this decline. NAR or HES were administrated orally (15mg/kg) to male 24-month-old Wistar rats during 4 weeks. Control groups received vehicle, sunflower oil. Qualitative and quantitative immunohistochemical and immunofluorescent expression of specific proteins and stereological analyses of thyroid tissue were performed. Thyroid stimulating hormone (TSH) and total thyroxine (T4) concentrations were measured in serum. Thyroid parenchyma of both flavanone-treated groups was characterized by lower (p<0.05) absolute and relative volume of luminal colloid, accompanied by elevated (p<0.05) relative volume of stroma in comparison with the controls. No hypertrophy or absolute thyroid volume change was detected. Intensity of immunopositive signal for thyroglobulin (Tg) and T4 bound to Tg (T4-Tg) increased (p<0.05) in the colloid of thyroid follicles after both flavanone treatments. Serum TSH increased (p<0.05) after NAR, while T4 remained unchanged after both treatments. In conclusion, NAR elevated serum TSH in old-aged males, thus being more potent than HES in altering pituitary-thyroid axis. However, changes in thyroid structure, namely moderate colloid depletion and higher Tg and T4-Tg protein expressions after both treatments, indicate preserved capacity of the gland to compensate flavanone interfering, and maintain T4 production in old-aged males.
T2  - Acta histochemica
T1  - Citrus flavanones mildly interfere with pituitary-thyroid axis in old-aged male rats.
IS  - 3
VL  - 119
DO  - 10.1016/j.acthis.2017.02.005
SP  - 292
EP  - 301
ER  - 

@article{
author = "Miler, Marko and Jarić, Ivana and Živanović, Jasmina and Ajdžanović, Vladimir and Tanić, Nasta and Milošević, Verica and Šošić-Jurjević, Branka ",
year = "2017",
abstract = "Citrus flavanones naringenin (NAR) and hesperetin (HES) are potent antioxidants that may contribute to maintenance of health at old age by improving cardiovascular and metabolic status. However, they may also affect thyroid hormone economy. Keeping in mind impaired thyroid function at older age, in this study we tested wheather NAR or HES administration potentiate this decline. NAR or HES were administrated orally (15mg/kg) to male 24-month-old Wistar rats during 4 weeks. Control groups received vehicle, sunflower oil. Qualitative and quantitative immunohistochemical and immunofluorescent expression of specific proteins and stereological analyses of thyroid tissue were performed. Thyroid stimulating hormone (TSH) and total thyroxine (T4) concentrations were measured in serum. Thyroid parenchyma of both flavanone-treated groups was characterized by lower (p<0.05) absolute and relative volume of luminal colloid, accompanied by elevated (p<0.05) relative volume of stroma in comparison with the controls. No hypertrophy or absolute thyroid volume change was detected. Intensity of immunopositive signal for thyroglobulin (Tg) and T4 bound to Tg (T4-Tg) increased (p<0.05) in the colloid of thyroid follicles after both flavanone treatments. Serum TSH increased (p<0.05) after NAR, while T4 remained unchanged after both treatments. In conclusion, NAR elevated serum TSH in old-aged males, thus being more potent than HES in altering pituitary-thyroid axis. However, changes in thyroid structure, namely moderate colloid depletion and higher Tg and T4-Tg protein expressions after both treatments, indicate preserved capacity of the gland to compensate flavanone interfering, and maintain T4 production in old-aged males.",
journal = "Acta histochemica",
title = "Citrus flavanones mildly interfere with pituitary-thyroid axis in old-aged male rats.",
number = "3",
volume = "119",
doi = "10.1016/j.acthis.2017.02.005",
pages = "292-301"
}

Miler, M., Jarić, I., Živanović, J., Ajdžanović, V., Tanić, N., Milošević, V.,& Šošić-Jurjević, B.. (2017). Citrus flavanones mildly interfere with pituitary-thyroid axis in old-aged male rats.. in Acta histochemica, 119(3), 292-301.
https://doi.org/10.1016/j.acthis.2017.02.005

Miler M, Jarić I, Živanović J, Ajdžanović V, Tanić N, Milošević V, Šošić-Jurjević B. Citrus flavanones mildly interfere with pituitary-thyroid axis in old-aged male rats.. in Acta histochemica. 2017;119(3):292-301.
doi:10.1016/j.acthis.2017.02.005 .

Miler, Marko, Jarić, Ivana, Živanović, Jasmina, Ajdžanović, Vladimir, Tanić, Nasta, Milošević, Verica, Šošić-Jurjević, Branka , "Citrus flavanones mildly interfere with pituitary-thyroid axis in old-aged male rats." in Acta histochemica, 119, no. 3 (2017):292-301,
https://doi.org/10.1016/j.acthis.2017.02.005 . .

TY  - JOUR
AU  - Tanić, Nasta
AU  - Milinković, Vedrana
AU  - Dramićanin, Tatjana
AU  - Nedeljković, Milica
AU  - Stanković, Tijana
AU  - Milovanović, Zorka
AU  - Šušnjar, Snežana
AU  - Milošević, Verica
AU  - Šošić-Jurjević, Branka 
AU  - Džodić, Radan
AU  - Tanić, Nikola
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/502
AB  - Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGfR), cyclinD1 (CCNDİ)and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential Pcr. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patient's outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients.
AB  - Uvod: Kancer dojke je najčešći tip maligniteta koji se javljaju kod žena. Tumori dojke nastaju kao rezultat akumulacije genetičkih promena kako u onkogenima tako i u tumor supresorskim genima. Među mnogim onkogenima čija je uloga u genezi tumora dojke ispitivana do danas, samo se neki smatraju značajnim za razviće ovih karcinoma. U tu se grupu svakako ubrajaju receptor za epidermalni factor rasta (EGFR), c-myc i ciklinD1 (CCND1). Cilj rada je bio utvrditi prognostički značaj amplifikacije CCND1, c-myc i EGFR onkogena u razviću tumora dojke kao i eventualne međusobne koalteracije ovih gena. Metode: Amplifikacioni status CCND1 i c-myc gena određen je kvantitativnim PCR-om u realnom vremenu, a amplifikacioni status EGFR onkogena je definisan diferencijalnim PCR-om. Rezultati: Amplifikacija CCND1 gena detektovana je kod 20.4%, a c-myc i EGFR onkogena kod 26.5% ispitanih uzoraka. Analize su pokazale da je amplifikacija CCND1 onkogena statistički značajno povezana sa stadijumom II tumora dojke kao i da amplifikacija EGFR-a značajno korelira sa povećanom ekspresijom HER2/neu. Analize kliničkih i histopatoloških parametara su jasno pokazale da stadijum tumora i nivo ekspresije HER2/neu gena predstavljaju značajne pokazatelje daljeg toka bolesti, odnosno sudbine pacijenta. Utvrđeno je da pacijentkinje sa tumorima dojke stadijuma I žive značajno duže od onih sa tumorom stadijuma III (p= 0.04) kao i da pacijentkinje sa HER2/neu pozitivnim statusom imaju goru prognozu i žive značajno krace (p=0.001). Na kraju, studija je pokazala da pacijentkinje podvrgnute samo hormonskoj terapiji imaju najbolju prognozu i žive značajno duže od ostalih (p=0.001). Zaključak: Amplifikacija CCND1 i EGFR onkogena je povezana sa lošom prognozom i progresijom karcinoma dojke. U ispitivanom tumorskom uzorku nisu detektovane nikakve koalteracije CCND1, c-myc i EGFR onkogena.
T2  - Journal of Medical Biochemistry
T1  - Amplifikacija ciklin D1, c-myc i EGFR onkogena u tumorskim uzorcima pacijentkinja obolelih od kancera dojke
T1  - Amplification of cycline D1, c-myc and EGFR oncogenes in tumour samples of breast cancer patients
IS  - 4
VL  - 32
DO  - 10.2478/jomb-2014-0005
SP  - 339
EP  - 346
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_502
ER  - 

@article{
author = "Tanić, Nasta and Milinković, Vedrana and Dramićanin, Tatjana and Nedeljković, Milica and Stanković, Tijana and Milovanović, Zorka and Šušnjar, Snežana and Milošević, Verica and Šošić-Jurjević, Branka  and Džodić, Radan and Tanić, Nikola",
year = "2013",
abstract = "Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGfR), cyclinD1 (CCNDİ)and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential Pcr. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patient's outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients., Uvod: Kancer dojke je najčešći tip maligniteta koji se javljaju kod žena. Tumori dojke nastaju kao rezultat akumulacije genetičkih promena kako u onkogenima tako i u tumor supresorskim genima. Među mnogim onkogenima čija je uloga u genezi tumora dojke ispitivana do danas, samo se neki smatraju značajnim za razviće ovih karcinoma. U tu se grupu svakako ubrajaju receptor za epidermalni factor rasta (EGFR), c-myc i ciklinD1 (CCND1). Cilj rada je bio utvrditi prognostički značaj amplifikacije CCND1, c-myc i EGFR onkogena u razviću tumora dojke kao i eventualne međusobne koalteracije ovih gena. Metode: Amplifikacioni status CCND1 i c-myc gena određen je kvantitativnim PCR-om u realnom vremenu, a amplifikacioni status EGFR onkogena je definisan diferencijalnim PCR-om. Rezultati: Amplifikacija CCND1 gena detektovana je kod 20.4%, a c-myc i EGFR onkogena kod 26.5% ispitanih uzoraka. Analize su pokazale da je amplifikacija CCND1 onkogena statistički značajno povezana sa stadijumom II tumora dojke kao i da amplifikacija EGFR-a značajno korelira sa povećanom ekspresijom HER2/neu. Analize kliničkih i histopatoloških parametara su jasno pokazale da stadijum tumora i nivo ekspresije HER2/neu gena predstavljaju značajne pokazatelje daljeg toka bolesti, odnosno sudbine pacijenta. Utvrđeno je da pacijentkinje sa tumorima dojke stadijuma I žive značajno duže od onih sa tumorom stadijuma III (p= 0.04) kao i da pacijentkinje sa HER2/neu pozitivnim statusom imaju goru prognozu i žive značajno krace (p=0.001). Na kraju, studija je pokazala da pacijentkinje podvrgnute samo hormonskoj terapiji imaju najbolju prognozu i žive značajno duže od ostalih (p=0.001). Zaključak: Amplifikacija CCND1 i EGFR onkogena je povezana sa lošom prognozom i progresijom karcinoma dojke. U ispitivanom tumorskom uzorku nisu detektovane nikakve koalteracije CCND1, c-myc i EGFR onkogena.",
journal = "Journal of Medical Biochemistry",
title = "Amplifikacija ciklin D1, c-myc i EGFR onkogena u tumorskim uzorcima pacijentkinja obolelih od kancera dojke, Amplification of cycline D1, c-myc and EGFR oncogenes in tumour samples of breast cancer patients",
number = "4",
volume = "32",
doi = "10.2478/jomb-2014-0005",
pages = "339-346",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_502"
}

Tanić, N., Milinković, V., Dramićanin, T., Nedeljković, M., Stanković, T., Milovanović, Z., Šušnjar, S., Milošević, V., Šošić-Jurjević, B., Džodić, R.,& Tanić, N.. (2013). Amplifikacija ciklin D1, c-myc i EGFR onkogena u tumorskim uzorcima pacijentkinja obolelih od kancera dojke. in Journal of Medical Biochemistry, 32(4), 339-346.
https://doi.org/10.2478/jomb-2014-0005
https://hdl.handle.net/21.15107/rcub_ibiss_502

Tanić N, Milinković V, Dramićanin T, Nedeljković M, Stanković T, Milovanović Z, Šušnjar S, Milošević V, Šošić-Jurjević B, Džodić R, Tanić N. Amplifikacija ciklin D1, c-myc i EGFR onkogena u tumorskim uzorcima pacijentkinja obolelih od kancera dojke. in Journal of Medical Biochemistry. 2013;32(4):339-346.
doi:10.2478/jomb-2014-0005
https://hdl.handle.net/21.15107/rcub_ibiss_502 .

Tanić, Nasta, Milinković, Vedrana, Dramićanin, Tatjana, Nedeljković, Milica, Stanković, Tijana, Milovanović, Zorka, Šušnjar, Snežana, Milošević, Verica, Šošić-Jurjević, Branka , Džodić, Radan, Tanić, Nikola, "Amplifikacija ciklin D1, c-myc i EGFR onkogena u tumorskim uzorcima pacijentkinja obolelih od kancera dojke" in Journal of Medical Biochemistry, 32, no. 4 (2013):339-346,
https://doi.org/10.2478/jomb-2014-0005 .,
https://hdl.handle.net/21.15107/rcub_ibiss_502 .

TY  - JOUR
AU  - Tanić, Nasta
AU  - Milašin, Jelena
AU  - Dramićanin, Tatjana
AU  - Bošković, Maja
AU  - Vukadinović, Miroslav
AU  - Milošević, Verica
AU  - Tanić, Nikola
PY  - 2013
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/505
AB  - Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. Therefore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycDI in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycDI and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours.
AB  - Uvod: Skvamocelularni karcinomi glave i vrata (HNSCC) uključujući i skvamocelularni karcinom usne duplje (OSCC) ubrajaju se u šest najčešćih tipova humanih maligniteta. Uprkos značajnim napredcima u hirurškom i terapijskom tretmanu, stopa petogodišnjeg preživljavanja kod ovog tipa maligniteta nije značajnije popravljena. Upravo zato, definisanje pouzdanih molekularnih markera progresije kod OSSC predstavlja apsolutni prioritetet. Metode: Amplifikacioni status c-myc, cycD1 i EGFR gena određen je pomoću eseja za detekciju broja genskih kopija, aktivacija H-ras onkogena i inaktivacija TP53 tumor supresora određena je PCR-SSCP mutacionom analizom, a hipermetilacija promotora p16 i MGMT gena je ispitana metil specifičnim PCR-om (MSP). Rezultati: Amplifikacija c-myc onkogena detektovana je kod 56,7%, cycD1 onkogena kod 20%, a EGFR onkogena kod 16,7% analiziranih oralnih skvamocelularnih carcinoma. Istovremeno, mutaciona aktivacija H-ras onkogena detektovana je kod 33,3% ispitanih uzoraka. Amplifikovani c-myc, statistički značajno korelira sa gradusom 2 OSCC. Posebno intrigantan je bio nalaz po kom se onkogene aktivacije u EGFR i H-ras genu međusobno isključuju. Hipermetilacija promotora p16 gena detektovana je kod 30%, a MGMT kod 13,3% analiziranih uzoraka. Ko-alteracije cycDI i p16 gena nisu zapažene ni u jednom od analiziranih uzoraka. Inaktivacija TP53 gena detektovana je kod 56,7% uzoraka i utvrđeno je da statistički značajno korelira sa gradusom 2 i statusom 2 OSCC. Pored ovoga, utvrđeno je da statistički značajan broj uzoraka gradusa 2, sa aktiviranim TP53 genom ima istovremeno aktiviran i c-myc onkogen. Zaključak: TP53, najčešće mutirani gen u oralnim karcinomima, ostaje za sada i najpouzdaniji marker progresije kod OSCC. Obzirom na detektovani sinergizam između TP53 i c-myc gena, možemo reći da su istovremene promene u ova dva gena još pouzdaniji pokazatelj progresije OSSC iz gradusa 1 u gradus 2.
T2  - Journal of Medical Biochemistry
T1  - Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma
T1  - TP53 and c-myc Co-alterations: A hallmark of oral cancer progression
IS  - 4
VL  - 32
SP  - 380
EP  - 388
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_505
ER  - 

@article{
author = "Tanić, Nasta and Milašin, Jelena and Dramićanin, Tatjana and Bošković, Maja and Vukadinović, Miroslav and Milošević, Verica and Tanić, Nikola",
year = "2013, 2013",
abstract = "Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. Therefore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to estimate amplification status of c-myc, cycD1 and EGFR oncogenes, mutational PCR-SSCP analysis to determine activation of H-ras oncogene and inactivation of TP53 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycDI in 20% and EGFR in 16.7% of Oral Squamous Cell Carcinoma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associated with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycDI and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP53 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC progression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP53 and c-myc, it seems that co-alteration of these two genes could be also a good marker of OSCC progression from grade1 to grade 2 tumours., Uvod: Skvamocelularni karcinomi glave i vrata (HNSCC) uključujući i skvamocelularni karcinom usne duplje (OSCC) ubrajaju se u šest najčešćih tipova humanih maligniteta. Uprkos značajnim napredcima u hirurškom i terapijskom tretmanu, stopa petogodišnjeg preživljavanja kod ovog tipa maligniteta nije značajnije popravljena. Upravo zato, definisanje pouzdanih molekularnih markera progresije kod OSSC predstavlja apsolutni prioritetet. Metode: Amplifikacioni status c-myc, cycD1 i EGFR gena određen je pomoću eseja za detekciju broja genskih kopija, aktivacija H-ras onkogena i inaktivacija TP53 tumor supresora određena je PCR-SSCP mutacionom analizom, a hipermetilacija promotora p16 i MGMT gena je ispitana metil specifičnim PCR-om (MSP). Rezultati: Amplifikacija c-myc onkogena detektovana je kod 56,7%, cycD1 onkogena kod 20%, a EGFR onkogena kod 16,7% analiziranih oralnih skvamocelularnih carcinoma. Istovremeno, mutaciona aktivacija H-ras onkogena detektovana je kod 33,3% ispitanih uzoraka. Amplifikovani c-myc, statistički značajno korelira sa gradusom 2 OSCC. Posebno intrigantan je bio nalaz po kom se onkogene aktivacije u EGFR i H-ras genu međusobno isključuju. Hipermetilacija promotora p16 gena detektovana je kod 30%, a MGMT kod 13,3% analiziranih uzoraka. Ko-alteracije cycDI i p16 gena nisu zapažene ni u jednom od analiziranih uzoraka. Inaktivacija TP53 gena detektovana je kod 56,7% uzoraka i utvrđeno je da statistički značajno korelira sa gradusom 2 i statusom 2 OSCC. Pored ovoga, utvrđeno je da statistički značajan broj uzoraka gradusa 2, sa aktiviranim TP53 genom ima istovremeno aktiviran i c-myc onkogen. Zaključak: TP53, najčešće mutirani gen u oralnim karcinomima, ostaje za sada i najpouzdaniji marker progresije kod OSCC. Obzirom na detektovani sinergizam između TP53 i c-myc gena, možemo reći da su istovremene promene u ova dva gena još pouzdaniji pokazatelj progresije OSSC iz gradusa 1 u gradus 2.",
journal = "Journal of Medical Biochemistry",
title = "Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma, TP53 and c-myc Co-alterations: A hallmark of oral cancer progression",
number = "4",
volume = "32",
pages = "380-388",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_505"
}

Tanić, N., Milašin, J., Dramićanin, T., Bošković, M., Vukadinović, M., Milošević, V.,& Tanić, N.. (2013). Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma. in Journal of Medical Biochemistry, 32(4), 380-388.
https://hdl.handle.net/21.15107/rcub_ibiss_505

Tanić N, Milašin J, Dramićanin T, Bošković M, Vukadinović M, Milošević V, Tanić N. Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma. in Journal of Medical Biochemistry. 2013;32(4):380-388.
https://hdl.handle.net/21.15107/rcub_ibiss_505 .

Tanić, Nasta, Milašin, Jelena, Dramićanin, Tatjana, Bošković, Maja, Vukadinović, Miroslav, Milošević, Verica, Tanić, Nikola, "Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma" in Journal of Medical Biochemistry, 32, no. 4 (2013):380-388,
https://hdl.handle.net/21.15107/rcub_ibiss_505 .

TY  - JOUR
AU  - Tanić, Nikola T
AU  - Milovanović, Zorka
AU  - Tanić, Nasta
AU  - Džodić, Radan R.
AU  - Juranić, Zorica D
AU  - Susnjar, Snezana
AU  - Plesinac-Karapandžić, Vesna
AU  - Tatić, Svetislav B
AU  - Dramicanin, Tatjana
AU  - Davidović, Radoslav
AU  - Dimitrijević, Bogomir B.
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1100
AB  - Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.
T2  - Cancer Biology & Therapy
T1  - The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients
IS  - 12
VL  - 13
SP  - 55
EP  - 1174
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1100
ER  - 

@article{
author = "Tanić, Nikola T and Milovanović, Zorka and Tanić, Nasta and Džodić, Radan R. and Juranić, Zorica D and Susnjar, Snezana and Plesinac-Karapandžić, Vesna and Tatić, Svetislav B and Dramicanin, Tatjana and Davidović, Radoslav and Dimitrijević, Bogomir B.",
year = "2012",
abstract = "Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen.",
journal = "Cancer Biology & Therapy",
title = "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients",
number = "12",
volume = "13",
pages = "55-1174",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1100"
}

Tanić, N. T., Milovanović, Z., Tanić, N., Džodić, R. R., Juranić, Z. D., Susnjar, S., Plesinac-Karapandžić, V., Tatić, S. B., Dramicanin, T., Davidović, R.,& Dimitrijević, B. B.. (2012). The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology & Therapy, 13(12), 55-1174.
https://hdl.handle.net/21.15107/rcub_ibiss_1100

Tanić NT, Milovanović Z, Tanić N, Džodić RR, Juranić ZD, Susnjar S, Plesinac-Karapandžić V, Tatić SB, Dramicanin T, Davidović R, Dimitrijević BB. The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients. in Cancer Biology & Therapy. 2012;13(12):55-1174.
https://hdl.handle.net/21.15107/rcub_ibiss_1100 .

Tanić, Nikola T, Milovanović, Zorka, Tanić, Nasta, Džodić, Radan R., Juranić, Zorica D, Susnjar, Snezana, Plesinac-Karapandžić, Vesna, Tatić, Svetislav B, Dramicanin, Tatjana, Davidović, Radoslav, Dimitrijević, Bogomir B., "The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients" in Cancer Biology & Therapy, 13, no. 12 (2012):55-1174,
https://hdl.handle.net/21.15107/rcub_ibiss_1100 .

TY  - JOUR
AU  - Roganović, Jelena
AU  - Radenković, Miroslav D
AU  - Tanić, Nikola T
AU  - Tanić, Nasta
AU  - Petrović, Nina
AU  - Stojić, Dragica D
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1258
AB  - The aim of this study was to assess the effect of type 1 diabetes mellitus (induced by a single intravenous injection of 100 mg kg(-1) of alloxan) on acetylcholine (ACh)-induced relaxation in isolated rabbit parotid gland feeding artery. Isometric force measurements and quantification of inducible nitric oxide synthase (iNOS) mRNA by real-time RT-PCR were made in parotid artery rings from diabetic and control rabbits. Acetylcholine induced concentration- and endothelium-dependent vasorelaxation that was significantly decreased in parotid artery rings from diabetic rabbits. Schild analysis of the ACh vasorelaxant effect, in the presence of selective muscarinic receptor antagonists, revealed involvement of the M(3) receptor subtype in parotid artery rings from both control and diabetic rabbits, with no change in antagonist affinity constants. The inhibitory effects of indomethacin, a non-selective inhibitor of cyclooxygenase, and of high potassium, an inhibitor of hyperpolarization, on ACh vasorelaxation were increased. The effect of N(G)-nitro-L-arginine, a non-selective inhibitor of NOS, was decreased in diabetes. S-methylisothiourea, a selective inhibitor of iNOS, significantly reduced ACh vasorelaxation only in parotid artery rings from diabetic rabbits. Also, up-regulation of iNOS mRNA expression was detected in parotid artery rings from diabetic rabbits. These results suggest that in parotid artery rings from diabetic rabbits, impaired endothelium-dependent vasorelaxation to ACh appears to be caused by the loss of a nitric oxide-mediated component and increased iNOS expression, and is unlikely to be caused by a change at the M(3) receptor level.
T2  - European Journal of Oral Sciences
T1  - Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit
IS  - 5
VL  - 119
EP  - 360
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1258
ER  - 

@article{
author = "Roganović, Jelena and Radenković, Miroslav D and Tanić, Nikola T and Tanić, Nasta and Petrović, Nina and Stojić, Dragica D",
year = "2011",
abstract = "The aim of this study was to assess the effect of type 1 diabetes mellitus (induced by a single intravenous injection of 100 mg kg(-1) of alloxan) on acetylcholine (ACh)-induced relaxation in isolated rabbit parotid gland feeding artery. Isometric force measurements and quantification of inducible nitric oxide synthase (iNOS) mRNA by real-time RT-PCR were made in parotid artery rings from diabetic and control rabbits. Acetylcholine induced concentration- and endothelium-dependent vasorelaxation that was significantly decreased in parotid artery rings from diabetic rabbits. Schild analysis of the ACh vasorelaxant effect, in the presence of selective muscarinic receptor antagonists, revealed involvement of the M(3) receptor subtype in parotid artery rings from both control and diabetic rabbits, with no change in antagonist affinity constants. The inhibitory effects of indomethacin, a non-selective inhibitor of cyclooxygenase, and of high potassium, an inhibitor of hyperpolarization, on ACh vasorelaxation were increased. The effect of N(G)-nitro-L-arginine, a non-selective inhibitor of NOS, was decreased in diabetes. S-methylisothiourea, a selective inhibitor of iNOS, significantly reduced ACh vasorelaxation only in parotid artery rings from diabetic rabbits. Also, up-regulation of iNOS mRNA expression was detected in parotid artery rings from diabetic rabbits. These results suggest that in parotid artery rings from diabetic rabbits, impaired endothelium-dependent vasorelaxation to ACh appears to be caused by the loss of a nitric oxide-mediated component and increased iNOS expression, and is unlikely to be caused by a change at the M(3) receptor level.",
journal = "European Journal of Oral Sciences",
title = "Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit",
number = "5",
volume = "119",
pages = "360",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1258"
}

Roganović, J., Radenković, M. D., Tanić, N. T., Tanić, N., Petrović, N.,& Stojić, D. D.. (2011). Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit. in European Journal of Oral Sciences, 119(5).
https://hdl.handle.net/21.15107/rcub_ibiss_1258

Roganović J, Radenković MD, Tanić NT, Tanić N, Petrović N, Stojić DD. Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit. in European Journal of Oral Sciences. 2011;119(5):null-360.
https://hdl.handle.net/21.15107/rcub_ibiss_1258 .

Roganović, Jelena, Radenković, Miroslav D, Tanić, Nikola T, Tanić, Nasta, Petrović, Nina, Stojić, Dragica D, "Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit" in European Journal of Oral Sciences, 119, no. 5 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1258 .

TY  - JOUR
AU  - Tanić, Nikola T
AU  - Stanojević, Boban R
AU  - Tanić, Nasta
AU  - Schaefer, Stephan
AU  - Niesters, Hubert GM
AU  - Bozić, Milena
AU  - Dimitrijević, Bogomir B.
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1424
AB  - Hepatitis B virus (HBV) infection is a global health problem associated with severe liver disorders. Viral load and HBV genotype affect the clinical outcome, guide antiviral therapy and provide long term prognosis for HBV infected patients. Various types of detection and quantitation assays are currently in use with a different effectiveness. The aim of this study was to develop a method that would provide simultaneous identification and quantitation of genotypes A and D in a single-tube reaction. Sera from infected patients were analyzed by a TaqMan based real time PCR. Optimized reagents were used for HBV DNA quantitation while the genotypes A and D were quantified separately by our design of the assay. Multiplex real time PCR was achieved and was specific for HBV genotypes A and D within a single-tube reaction. Simulation of mixed virus populations was identified reproducibly in vitro. Quantitation of these individual genotypes was exceptionally reliable, so much so that the sum of individual genotypes was equal to the total viral load determined in a separate reaction. Therefore, a straightforward, conceptually simple and reliable approach to issues involving HBV genotypes A and D is submitted. Identity and exact titer of these genotypes in the Caucasian population can now be determined easily. (C) 2009 Elsevier B.V. All rights reserved.
T2  - Journal of Virological Methods
T1  - Concurrent quantitation of the A and D genotypes of hepatitis B virus
IS  - 2
VL  - 161
EP  - 270
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1424
ER  - 

@article{
author = "Tanić, Nikola T and Stanojević, Boban R and Tanić, Nasta and Schaefer, Stephan and Niesters, Hubert GM and Bozić, Milena and Dimitrijević, Bogomir B.",
year = "2009",
abstract = "Hepatitis B virus (HBV) infection is a global health problem associated with severe liver disorders. Viral load and HBV genotype affect the clinical outcome, guide antiviral therapy and provide long term prognosis for HBV infected patients. Various types of detection and quantitation assays are currently in use with a different effectiveness. The aim of this study was to develop a method that would provide simultaneous identification and quantitation of genotypes A and D in a single-tube reaction. Sera from infected patients were analyzed by a TaqMan based real time PCR. Optimized reagents were used for HBV DNA quantitation while the genotypes A and D were quantified separately by our design of the assay. Multiplex real time PCR was achieved and was specific for HBV genotypes A and D within a single-tube reaction. Simulation of mixed virus populations was identified reproducibly in vitro. Quantitation of these individual genotypes was exceptionally reliable, so much so that the sum of individual genotypes was equal to the total viral load determined in a separate reaction. Therefore, a straightforward, conceptually simple and reliable approach to issues involving HBV genotypes A and D is submitted. Identity and exact titer of these genotypes in the Caucasian population can now be determined easily. (C) 2009 Elsevier B.V. All rights reserved.",
journal = "Journal of Virological Methods",
title = "Concurrent quantitation of the A and D genotypes of hepatitis B virus",
number = "2",
volume = "161",
pages = "270",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1424"
}

Tanić, N. T., Stanojević, B. R., Tanić, N., Schaefer, S., Niesters, H. G., Bozić, M.,& Dimitrijević, B. B.. (2009). Concurrent quantitation of the A and D genotypes of hepatitis B virus. in Journal of Virological Methods, 161(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1424

Tanić NT, Stanojević BR, Tanić N, Schaefer S, Niesters HG, Bozić M, Dimitrijević BB. Concurrent quantitation of the A and D genotypes of hepatitis B virus. in Journal of Virological Methods. 2009;161(2):null-270.
https://hdl.handle.net/21.15107/rcub_ibiss_1424 .

Tanić, Nikola T, Stanojević, Boban R, Tanić, Nasta, Schaefer, Stephan, Niesters, Hubert GM, Bozić, Milena, Dimitrijević, Bogomir B., "Concurrent quantitation of the A and D genotypes of hepatitis B virus" in Journal of Virological Methods, 161, no. 2 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1424 .

TY  - JOUR
AU  - Tanić, Nasta
AU  - Tanić, Nikola T
AU  - Milasin, Jelena M
AU  - Vukadinović, Miroslav
AU  - Dimitrijević, Bogomir B.
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1448
AB  - Leukoplakias, clinically identifiable premalignant lesions, often precede oral squamous cell carcinoma (OSCC). Identification of leukoplakias that have the potential for transformation to malignancy is a key clinical problem. The aim of this study was to assess genomic instability, and to detect tumor-specific genomic alterations, in leukoplakias. Genomic instability was analyzed by comparing the DNA fingerprints of 32 leukoplakias with those of paired normal tissue. In addition, the mutational status of the p53 gene was analyzed using polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) and polymerase chain reaction-heteroduplex DNA (PCR-HET), and the mutations were subsequently confirmed by DNA sequencing. Moderate-to-significant genomic instability was detected in all leukoplakias analysed. Nine unique amplicons, present in leukoplakias but not in normal tissue, were retrieved and successfully characterized. The p53 gene was mutated in 40.6% of patients. Four patients with moderate instability and mutated p53 developed OSCC. The data obtained in this study support and concretize the thesis that premalignant lesions possess many of the alterations found in cancer before the development of a malignant phenotype. Inactivation or mutation of the p53 tumor-suppressor might be an early event contributing to genomic instability and increasing the risk of malignant transformation.
T2  - European Journal of Oral Sciences
T1  - Genomic instability and tumor-specific DNA alterations in oral leukoplakias
IS  - 3
VL  - 117
EP  - 237
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1448
ER  - 

@article{
author = "Tanić, Nasta and Tanić, Nikola T and Milasin, Jelena M and Vukadinović, Miroslav and Dimitrijević, Bogomir B.",
year = "2009",
abstract = "Leukoplakias, clinically identifiable premalignant lesions, often precede oral squamous cell carcinoma (OSCC). Identification of leukoplakias that have the potential for transformation to malignancy is a key clinical problem. The aim of this study was to assess genomic instability, and to detect tumor-specific genomic alterations, in leukoplakias. Genomic instability was analyzed by comparing the DNA fingerprints of 32 leukoplakias with those of paired normal tissue. In addition, the mutational status of the p53 gene was analyzed using polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) and polymerase chain reaction-heteroduplex DNA (PCR-HET), and the mutations were subsequently confirmed by DNA sequencing. Moderate-to-significant genomic instability was detected in all leukoplakias analysed. Nine unique amplicons, present in leukoplakias but not in normal tissue, were retrieved and successfully characterized. The p53 gene was mutated in 40.6% of patients. Four patients with moderate instability and mutated p53 developed OSCC. The data obtained in this study support and concretize the thesis that premalignant lesions possess many of the alterations found in cancer before the development of a malignant phenotype. Inactivation or mutation of the p53 tumor-suppressor might be an early event contributing to genomic instability and increasing the risk of malignant transformation.",
journal = "European Journal of Oral Sciences",
title = "Genomic instability and tumor-specific DNA alterations in oral leukoplakias",
number = "3",
volume = "117",
pages = "237",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1448"
}

Tanić, N., Tanić, N. T., Milasin, J. M., Vukadinović, M.,& Dimitrijević, B. B.. (2009). Genomic instability and tumor-specific DNA alterations in oral leukoplakias. in European Journal of Oral Sciences, 117(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1448

Tanić N, Tanić NT, Milasin JM, Vukadinović M, Dimitrijević BB. Genomic instability and tumor-specific DNA alterations in oral leukoplakias. in European Journal of Oral Sciences. 2009;117(3):null-237.
https://hdl.handle.net/21.15107/rcub_ibiss_1448 .

Tanić, Nasta, Tanić, Nikola T, Milasin, Jelena M, Vukadinović, Miroslav, Dimitrijević, Bogomir B., "Genomic instability and tumor-specific DNA alterations in oral leukoplakias" in European Journal of Oral Sciences, 117, no. 3 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1448 .