TY  - CONF
AU  - Kožik, Bojana
AU  - Todorović, Lidija
AU  - Božović, Ana
AU  - Kolaković, Ana
AU  - Vasiljević, Tijana
AU  - Đurić, Mladen
AU  - Đermanović, Aleksandar
AU  - Mandušić, Vesna
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13104
AB  - Introduction: Venous invasion has consistently been shown to be associated with poor prognosis in rectal carcinoma (RC), both when detected by pathology and radiology. Extramural venous invasion (EMVI) is characterized by the presence of tumor cells within veins outside the bowel wall and is strongly associated with poor survival and increased risk of local recurrence and distant metastases. Molecular basis of EMVI is still unexplored and genes that regulate tumor microenvironment interactions may have significant role in this process. ZEB1 is transcriptional factor that promote cancerogenesis by indirect regulation of epithelial-mesenchymal transition (EMT) process, while LOXL2 contributes to tumor invasion and metastasis due to its role in the stabilization of the extracellular matrix. Aim: This study aimed to compare the expression level of ZEB1 and LOXL2 genes in relation to EMVI status and other clinic-pathological parameters of RC patients. Methods: We conducted preliminary study on 21 untreated RC patients (9 EMVI+ and 11 EMVI- ) who underwent curative resection in 2016-2018 at Oncology Institute of Vojvodina. The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological sections of postoperative tumor specimen samples, from which RNA was isolated. Expression of ZEB1 and LOXL2 mRNA was measured using quantitative real-time PCR. Results: Comparative analysis revealed higher expression level of ZEB1 in EMVI positive samples and in patients in TNMIII stage, however the observed differences had no statistic significance (p=0.323 and p=0.197, respectively). Significant difference in LOXL2 expression according to the EMVI status was not detected (p=0.915), while we noted higher LOXL2 expression in late stages of disease, but without statistic significance (p=0.342). Relative expression of these two genes was not associated with metastases frequency and death outcome. Conclusion: Further analyses on larger number of samples with more potential molecular targets included are required and planed.
AB  - Uvod: Venska invazija je kontinuirano asocirana sa lošom prognozom kod obolelih od karcinoma rektuma (KR), bilo da je detektovana patološkim ili radiološkim metodama. Ekstramuralna venska invazija (EMVI) se karakteriše kao prisustvo tumorskih ćelija u venskim sudovima izvan zida debelog creva koje je značajno asocirano sa lošim preživljavanjem i povećanim rizikom za nastanak lokalnih recidiva i udaljenih metastaza. Molekularna osnova EMVI procesa nije dovoljno ispitana, a geni koji regulišu interakcije u tumorskoj mikrosredini mogu imati potencijalnu ulogu. ZEB1 je transkripcioni factor koji stimuliše kancerogenezu indirektnom regulacijom epitelnomezenhimske tranzicije (EMT), dok LOXL2 doprinosi procesu tumorske invazije ulogom u stabilizaciji ektracelularnog matriksa. Cilj: Cilj ove studije je uporediti relativnu ekspresije gena ZEB1 i LOXL2 u odnosu na EMVI status i druge kliničko-patološke parametre KR pacijenta. Metode: Ova preliminarna studija obuhvatila je 21 netretiranih KR pacijenata (9 EMVI+ i 11 EMVI-) koji su lečeni operativnim putem u periodu 2016-2018. god. u Institutu za onkologiju Vojvodina. Prisustvo EMVI je utvrđeno na standardno hematoksilinom i eozinom bojenim isečcima postoperativnog tumorskog tkiva iz kojih je izolovana RNK. Ekspresija ZEB1 i LOXL2 iRNA izmerena je kvantitativnom PCR metodom u realnom vremenu. Rezultati: Uporednom analizom uočena je povišena ekspresija ZEB1 kod EMVI+ uzoraka i kod obolelih u TNMIII stadijumu, ali uočene razlike nisu bile statistički značajne (p=0,323 i p=0,197, respektivno). Znčajna razlika u ekspresiji LOXL2 u odnosu na EMVI status nije detektovana (p=0,915), a zabeležena je i povećana ekspresija LOXL2 u kasnim stadijumima bolesti, ali bez statističke značajnosti (p=0,342). Relativna ekspresija ova dva gena nije značajno povezana sa pojavom metstaza i krajnjim ishodom bolesti. Zaključak: Dalje analize na većem broju uzoraka sa više uključenih molekularnih targeta u studiju su neophodne i planirane u budućnosti.
PB  - Belgrade : Serbian Medical Society Oncology Section
C3  - Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata
T1  - Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study
T1  - Ekspresija ZEB1 i LOXL2 gena kod karcinoma rektuma i njihova korelacija sa ekstramuralnom venskom invazijom (EMVI): preliminarna studija
UR  - https://hdl.handle.net/21.15107/rcub_vinar_13104
ER  - 

@conference{
author = "Kožik, Bojana and Todorović, Lidija and Božović, Ana and Kolaković, Ana and Vasiljević, Tijana and Đurić, Mladen and Đermanović, Aleksandar and Mandušić, Vesna",
year = "2023",
abstract = "Introduction: Venous invasion has consistently been shown to be associated with poor prognosis in rectal carcinoma (RC), both when detected by pathology and radiology. Extramural venous invasion (EMVI) is characterized by the presence of tumor cells within veins outside the bowel wall and is strongly associated with poor survival and increased risk of local recurrence and distant metastases. Molecular basis of EMVI is still unexplored and genes that regulate tumor microenvironment interactions may have significant role in this process. ZEB1 is transcriptional factor that promote cancerogenesis by indirect regulation of epithelial-mesenchymal transition (EMT) process, while LOXL2 contributes to tumor invasion and metastasis due to its role in the stabilization of the extracellular matrix. Aim: This study aimed to compare the expression level of ZEB1 and LOXL2 genes in relation to EMVI status and other clinic-pathological parameters of RC patients. Methods: We conducted preliminary study on 21 untreated RC patients (9 EMVI+ and 11 EMVI- ) who underwent curative resection in 2016-2018 at Oncology Institute of Vojvodina. The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological sections of postoperative tumor specimen samples, from which RNA was isolated. Expression of ZEB1 and LOXL2 mRNA was measured using quantitative real-time PCR. Results: Comparative analysis revealed higher expression level of ZEB1 in EMVI positive samples and in patients in TNMIII stage, however the observed differences had no statistic significance (p=0.323 and p=0.197, respectively). Significant difference in LOXL2 expression according to the EMVI status was not detected (p=0.915), while we noted higher LOXL2 expression in late stages of disease, but without statistic significance (p=0.342). Relative expression of these two genes was not associated with metastases frequency and death outcome. Conclusion: Further analyses on larger number of samples with more potential molecular targets included are required and planed., Uvod: Venska invazija je kontinuirano asocirana sa lošom prognozom kod obolelih od karcinoma rektuma (KR), bilo da je detektovana patološkim ili radiološkim metodama. Ekstramuralna venska invazija (EMVI) se karakteriše kao prisustvo tumorskih ćelija u venskim sudovima izvan zida debelog creva koje je značajno asocirano sa lošim preživljavanjem i povećanim rizikom za nastanak lokalnih recidiva i udaljenih metastaza. Molekularna osnova EMVI procesa nije dovoljno ispitana, a geni koji regulišu interakcije u tumorskoj mikrosredini mogu imati potencijalnu ulogu. ZEB1 je transkripcioni factor koji stimuliše kancerogenezu indirektnom regulacijom epitelnomezenhimske tranzicije (EMT), dok LOXL2 doprinosi procesu tumorske invazije ulogom u stabilizaciji ektracelularnog matriksa. Cilj: Cilj ove studije je uporediti relativnu ekspresije gena ZEB1 i LOXL2 u odnosu na EMVI status i druge kliničko-patološke parametre KR pacijenta. Metode: Ova preliminarna studija obuhvatila je 21 netretiranih KR pacijenata (9 EMVI+ i 11 EMVI-) koji su lečeni operativnim putem u periodu 2016-2018. god. u Institutu za onkologiju Vojvodina. Prisustvo EMVI je utvrđeno na standardno hematoksilinom i eozinom bojenim isečcima postoperativnog tumorskog tkiva iz kojih je izolovana RNK. Ekspresija ZEB1 i LOXL2 iRNA izmerena je kvantitativnom PCR metodom u realnom vremenu. Rezultati: Uporednom analizom uočena je povišena ekspresija ZEB1 kod EMVI+ uzoraka i kod obolelih u TNMIII stadijumu, ali uočene razlike nisu bile statistički značajne (p=0,323 i p=0,197, respektivno). Znčajna razlika u ekspresiji LOXL2 u odnosu na EMVI status nije detektovana (p=0,915), a zabeležena je i povećana ekspresija LOXL2 u kasnim stadijumima bolesti, ali bez statističke značajnosti (p=0,342). Relativna ekspresija ova dva gena nije značajno povezana sa pojavom metstaza i krajnjim ishodom bolesti. Zaključak: Dalje analize na većem broju uzoraka sa više uključenih molekularnih targeta u studiju su neophodne i planirane u budućnosti.",
publisher = "Belgrade : Serbian Medical Society Oncology Section",
journal = "Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata",
title = "Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study, Ekspresija ZEB1 i LOXL2 gena kod karcinoma rektuma i njihova korelacija sa ekstramuralnom venskom invazijom (EMVI): preliminarna studija",
url = "https://hdl.handle.net/21.15107/rcub_vinar_13104"
}

Kožik, B., Todorović, L., Božović, A., Kolaković, A., Vasiljević, T., Đurić, M., Đermanović, A.,& Mandušić, V.. (2023). Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study. in Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata
Belgrade : Serbian Medical Society Oncology Section..
https://hdl.handle.net/21.15107/rcub_vinar_13104

Kožik B, Todorović L, Božović A, Kolaković A, Vasiljević T, Đurić M, Đermanović A, Mandušić V. Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study. in Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata. 2023;.
https://hdl.handle.net/21.15107/rcub_vinar_13104 .

Kožik, Bojana, Todorović, Lidija, Božović, Ana, Kolaković, Ana, Vasiljević, Tijana, Đurić, Mladen, Đermanović, Aleksandar, Mandušić, Vesna, "Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study" in Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata (2023),
https://hdl.handle.net/21.15107/rcub_vinar_13104 .

TY  - CONF
AU  - Božović, Ana
AU  - Mandušić, Vesna
AU  - Todorović, Lidija
AU  - Krajnović, Milena
AU  - Kožik, Bojana
AU  - Jovanović-Ćupić, Snežana
AU  - Kokanov, Nikola
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12632
AB  - Since the estrogen receptor alpha (ERα), together with the progesterone receptor (PR) and the hercepƟ n receptor 2 (HER-2), are the dominant factors determining the groups of breast cancer (BC) paƟ ents, breast cancer treatment depends on the presence or absence of these three molecules. Approximately 70% of paƟ ents receive hormone treatment targeƟ ng the estrogen receptor alfa, with tamoxifen (selecƟ ve oestrogen receptor modulator) being the fi rst choice as it inhibits further proliferaƟ on of cancer cells. However, 30% of paƟ ents do not respond to exisƟ ng hormone therapy, raising the quesƟ on of new targets and treatment opƟ ons. Non-responders include paƟ ents who have acquired resistance to standard treatment and triple-negaƟ ve breast cancer paƟ ents (TNBC), characterized by the absence of ERα, PR and HER-2. One of the unexplored potenƟ als for treatment is a protein homologue of ERα, estrogen receptor beta (ERβ), as many studies show ERβ expression in ERα-negaƟ ve paƟ ents. The estrogen receptors alpha and beta belong to the superfamily of nuclear receptors, and their dominant ligand is estrogen. When estrogen binds to estrogen receptors, they form dimers (homo or heterodimers) and bind ERE sequences of target genes (estrogen receptor elements). In a heterodimeric state, ERβ can inhibit ERα transacƟ vaƟ on and thus infl uence the signalling pathways. ERα and ERβ are encoded by highly homologous genes (ESR1 and ESR2), resulƟ ng in two highly homologous protein structures. The human ESR2 gene contains eight exons. The last two coding exons of the ESR2 gene are alternaƟ vely spliced encoding ERβ transcripƟ onal variants (ERβ1-5), resulƟ ng in altered C-terminal domains of the ERβ protein. These transcripƟ onal variants can have dominant posiƟ ve or negaƟ ve funcƟ ons or no funcƟ on at all. While ERα is crucial for the growth and proliferaƟ on of breast Ɵ ssue, ERꞵ plays a role in the normal development of breast Ɵ ssue, ovaries, testes, brain and adrenal glands. Study reports show that ERβ has an anƟ proliferaƟ ve, pro-apoptoƟ c and tumour-suppressive funcƟ on. Its funcƟ on in breast development also implies its funcƟ on in tumourigenesis. However, the expression of ERβ mRNA and protein expression is unclear. Various studies on ERα-posiƟ ve tumours show that ERβ is a tumour suppressor. The studies on ERα-negaƟ ve tumours show controversy, whereby ERβ could be proliferaƟ ve or suppressive. ERβ expression is oŌ en associated with smaller tumour size, lower grade and the absence of metastases. In TNBC paƟ ents, the associaƟ on between clinical outcomes and ERβ is unclear. Some studies associate ERβ with prolonged survival, others with shortened survival, while in others, no associaƟ on has been demonstrated. There are many reasons for these contradicƟ ons. The fi rst reason is unprecise methods of measuring ERβ levels, with diff erences in baseline material. In some studies, the amount of ERβ is esƟ mated by quanƟ taƟ ve PCR, while in others, by anƟ bodies. Secondly, the researchers prevalently use non-specifi c anƟ bodies that cannot detect the existence of specifi c ERβ isoforms. ERβ expression changes during BC progression. In the early stages of BC, ERβ levels decrease, while more advanced stages show a complete loss of ERβ. However, some studies report increased ERβ expression in metastaƟ c Ɵ ssues. Researchers should pay parƟ cular aƩ enƟ on to the molecular mechanisms that alter ERβ expression, with epigeneƟ c mechanisms being the most crucial. One of the most important mechanisms for tumour iniƟ aƟ on and development is gene promoter methylaƟ on. DNA methylaƟ on is an inheritable epigeneƟ c modifi caƟ on in which DNA methyltransferases (DNMTs) promote the transfer of the methyl group from S-adenosyl L-methionine (SAM) to 5'-cytosine of the CpG dinucleoƟ de. CpG methylaƟ on is a crucial regulatory mechanism that begins early in embryogenesis. In the promoters of genes central to development, such as housekeeping genes and some Ɵ ssue-specifi c genes, there are unmethylated regions called CpG islands. CpG islands encompass about 500 to several thousands of base pairs, and the CpGdinucleoƟ des within them are more abundant than in the other genome locaƟ ons. CpG islands in coding genes' promoter regions of cancer cells are regularly hypermethylated, causing gene silencing. The silenced genes are commonly tumour suppressor genes, such as ERβ. ERβ gene promoter region contains two exons, exon OK and exon ON. Most studies have been done on ON exon, linking hypermethylaƟ on of ON exon with decreased ERβ expression. IniƟ ally, the researchers noƟ ced ON exon hypermethylaƟ on in prostate cancer, and prostate cancer cell treatment with a demethylaƟ on agent, 5'-AZAC, led to ERβ expression acƟ vaƟ on. Also, during the progression of prostate cancer, a hypermethylaƟ on level increased. These results were consistent with some studies on breast cancer paƟ ents and cell lines. There is scant data on the associaƟ on between ERβ hypermethylaƟ on and surv ival. Usually, studies show correlaƟ ons between ERβ1 expression and survival. The clinical potenƟ al of ERβ promoter methylaƟ on is yet to be examined. AddiƟ onal research on this molecule and its expression mechanisms should determine its predicƟ ve, diagnosƟ c, and treatment potenƟ al.
PB  - Belgrade : Serbian Association for Cancer Research
C3  - Oncology Insights
T1  - Estrogen Receptor Beta promoter methylation as a possible biomarker in breast cancer
IS  - 1
SP  - 26
EP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12632
ER  - 

@conference{
author = "Božović, Ana and Mandušić, Vesna and Todorović, Lidija and Krajnović, Milena and Kožik, Bojana and Jovanović-Ćupić, Snežana and Kokanov, Nikola",
year = "2023",
abstract = "Since the estrogen receptor alpha (ERα), together with the progesterone receptor (PR) and the hercepƟ n receptor 2 (HER-2), are the dominant factors determining the groups of breast cancer (BC) paƟ ents, breast cancer treatment depends on the presence or absence of these three molecules. Approximately 70% of paƟ ents receive hormone treatment targeƟ ng the estrogen receptor alfa, with tamoxifen (selecƟ ve oestrogen receptor modulator) being the fi rst choice as it inhibits further proliferaƟ on of cancer cells. However, 30% of paƟ ents do not respond to exisƟ ng hormone therapy, raising the quesƟ on of new targets and treatment opƟ ons. Non-responders include paƟ ents who have acquired resistance to standard treatment and triple-negaƟ ve breast cancer paƟ ents (TNBC), characterized by the absence of ERα, PR and HER-2. One of the unexplored potenƟ als for treatment is a protein homologue of ERα, estrogen receptor beta (ERβ), as many studies show ERβ expression in ERα-negaƟ ve paƟ ents. The estrogen receptors alpha and beta belong to the superfamily of nuclear receptors, and their dominant ligand is estrogen. When estrogen binds to estrogen receptors, they form dimers (homo or heterodimers) and bind ERE sequences of target genes (estrogen receptor elements). In a heterodimeric state, ERβ can inhibit ERα transacƟ vaƟ on and thus infl uence the signalling pathways. ERα and ERβ are encoded by highly homologous genes (ESR1 and ESR2), resulƟ ng in two highly homologous protein structures. The human ESR2 gene contains eight exons. The last two coding exons of the ESR2 gene are alternaƟ vely spliced encoding ERβ transcripƟ onal variants (ERβ1-5), resulƟ ng in altered C-terminal domains of the ERβ protein. These transcripƟ onal variants can have dominant posiƟ ve or negaƟ ve funcƟ ons or no funcƟ on at all. While ERα is crucial for the growth and proliferaƟ on of breast Ɵ ssue, ERꞵ plays a role in the normal development of breast Ɵ ssue, ovaries, testes, brain and adrenal glands. Study reports show that ERβ has an anƟ proliferaƟ ve, pro-apoptoƟ c and tumour-suppressive funcƟ on. Its funcƟ on in breast development also implies its funcƟ on in tumourigenesis. However, the expression of ERβ mRNA and protein expression is unclear. Various studies on ERα-posiƟ ve tumours show that ERβ is a tumour suppressor. The studies on ERα-negaƟ ve tumours show controversy, whereby ERβ could be proliferaƟ ve or suppressive. ERβ expression is oŌ en associated with smaller tumour size, lower grade and the absence of metastases. In TNBC paƟ ents, the associaƟ on between clinical outcomes and ERβ is unclear. Some studies associate ERβ with prolonged survival, others with shortened survival, while in others, no associaƟ on has been demonstrated. There are many reasons for these contradicƟ ons. The fi rst reason is unprecise methods of measuring ERβ levels, with diff erences in baseline material. In some studies, the amount of ERβ is esƟ mated by quanƟ taƟ ve PCR, while in others, by anƟ bodies. Secondly, the researchers prevalently use non-specifi c anƟ bodies that cannot detect the existence of specifi c ERβ isoforms. ERβ expression changes during BC progression. In the early stages of BC, ERβ levels decrease, while more advanced stages show a complete loss of ERβ. However, some studies report increased ERβ expression in metastaƟ c Ɵ ssues. Researchers should pay parƟ cular aƩ enƟ on to the molecular mechanisms that alter ERβ expression, with epigeneƟ c mechanisms being the most crucial. One of the most important mechanisms for tumour iniƟ aƟ on and development is gene promoter methylaƟ on. DNA methylaƟ on is an inheritable epigeneƟ c modifi caƟ on in which DNA methyltransferases (DNMTs) promote the transfer of the methyl group from S-adenosyl L-methionine (SAM) to 5'-cytosine of the CpG dinucleoƟ de. CpG methylaƟ on is a crucial regulatory mechanism that begins early in embryogenesis. In the promoters of genes central to development, such as housekeeping genes and some Ɵ ssue-specifi c genes, there are unmethylated regions called CpG islands. CpG islands encompass about 500 to several thousands of base pairs, and the CpGdinucleoƟ des within them are more abundant than in the other genome locaƟ ons. CpG islands in coding genes' promoter regions of cancer cells are regularly hypermethylated, causing gene silencing. The silenced genes are commonly tumour suppressor genes, such as ERβ. ERβ gene promoter region contains two exons, exon OK and exon ON. Most studies have been done on ON exon, linking hypermethylaƟ on of ON exon with decreased ERβ expression. IniƟ ally, the researchers noƟ ced ON exon hypermethylaƟ on in prostate cancer, and prostate cancer cell treatment with a demethylaƟ on agent, 5'-AZAC, led to ERβ expression acƟ vaƟ on. Also, during the progression of prostate cancer, a hypermethylaƟ on level increased. These results were consistent with some studies on breast cancer paƟ ents and cell lines. There is scant data on the associaƟ on between ERβ hypermethylaƟ on and surv ival. Usually, studies show correlaƟ ons between ERβ1 expression and survival. The clinical potenƟ al of ERβ promoter methylaƟ on is yet to be examined. AddiƟ onal research on this molecule and its expression mechanisms should determine its predicƟ ve, diagnosƟ c, and treatment potenƟ al.",
publisher = "Belgrade : Serbian Association for Cancer Research",
journal = "Oncology Insights",
title = "Estrogen Receptor Beta promoter methylation as a possible biomarker in breast cancer",
number = "1",
pages = "26-27",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12632"
}

Božović, A., Mandušić, V., Todorović, L., Krajnović, M., Kožik, B., Jovanović-Ćupić, S.,& Kokanov, N.. (2023). Estrogen Receptor Beta promoter methylation as a possible biomarker in breast cancer. in Oncology Insights
Belgrade : Serbian Association for Cancer Research.(1), 26-27.
https://hdl.handle.net/21.15107/rcub_vinar_12632

Božović A, Mandušić V, Todorović L, Krajnović M, Kožik B, Jovanović-Ćupić S, Kokanov N. Estrogen Receptor Beta promoter methylation as a possible biomarker in breast cancer. in Oncology Insights. 2023;(1):26-27.
https://hdl.handle.net/21.15107/rcub_vinar_12632 .

Božović, Ana, Mandušić, Vesna, Todorović, Lidija, Krajnović, Milena, Kožik, Bojana, Jovanović-Ćupić, Snežana, Kokanov, Nikola, "Estrogen Receptor Beta promoter methylation as a possible biomarker in breast cancer" in Oncology Insights, no. 1 (2023):26-27,
https://hdl.handle.net/21.15107/rcub_vinar_12632 .

TY  - JOUR
AU  - Krajnović, Milena M.
AU  - Kožik, Bojana
AU  - Božović, Ana M.
AU  - Jovanović-Ćupić, Snežana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11625
AB  - : Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by a high resistance to conventional chemotherapy, late diagnosis, and a high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and plays paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors and depends on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.
T2  - Cells
T1  - Multiple Roles of the RUNX Gene Family in Hepatocellular Carcinoma and Their Potential Clinical Implications
VL  - 12
IS  - 18
SP  - 2303
DO  - 10.3390/cells12182303
ER  - 

@article{
author = "Krajnović, Milena M. and Kožik, Bojana and Božović, Ana M. and Jovanović-Ćupić, Snežana",
year = "2023",
abstract = ": Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by a high resistance to conventional chemotherapy, late diagnosis, and a high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and plays paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors and depends on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.",
journal = "Cells",
title = "Multiple Roles of the RUNX Gene Family in Hepatocellular Carcinoma and Their Potential Clinical Implications",
volume = "12",
number = "18",
pages = "2303",
doi = "10.3390/cells12182303"
}

Krajnović, M. M., Kožik, B., Božović, A. M.,& Jovanović-Ćupić, S.. (2023). Multiple Roles of the RUNX Gene Family in Hepatocellular Carcinoma and Their Potential Clinical Implications. in Cells, 12(18), 2303.
https://doi.org/10.3390/cells12182303

Krajnović MM, Kožik B, Božović AM, Jovanović-Ćupić S. Multiple Roles of the RUNX Gene Family in Hepatocellular Carcinoma and Their Potential Clinical Implications. in Cells. 2023;12(18):2303.
doi:10.3390/cells12182303 .

Krajnović, Milena M., Kožik, Bojana, Božović, Ana M., Jovanović-Ćupić, Snežana, "Multiple Roles of the RUNX Gene Family in Hepatocellular Carcinoma and Their Potential Clinical Implications" in Cells, 12, no. 18 (2023):2303,
https://doi.org/10.3390/cells12182303 . .

TY  - JOUR
AU  - Kokanov, Nikola
AU  - Krajnović, Milena M.
AU  - Jovanović-Ćupić, Snežana P.
AU  - Kožik, Bojana
AU  - Petrović, Nina
AU  - Božović, Ana M.
AU  - Mandušić, Vesna
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10273
AB  - Prevention of chronic hepatitis C (CHC) and its complications is based on antiviral therapy and early detection of reliable molecular markers in persons under risk. We investigated whether the methylation status of RASSF1A and p16 genes, alone or in combination with host and viral factors, affects the response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV). Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of the target promoter sequences of RASSF1A and p16 in circulating-free DNA from the peripheral blood of 49 patients with CHC genotype 1b. The methylation status of the examined genes did not affect the response to therapy. However, the simultaneous presence of either RASSF1A or p16 methylation and the CC genotype of IL28B was significantly related to a sustained virologic response (P=0.009 and P=0.032, respectively). After Bonferroni correction, only the result concerning the RASSF1A gene remained significant (P<0.0125). Methylation of RASSF1A was associated with the CC genotype of the IL28B gene (P=0.024) and a higher viral load (≥400 000 IU/mL, P=0.009). Our results suggest that combined analysis of RASSF1A gene methylation and IL28B rs12979860 polymorphism could potentially help in the prediction of therapy response in CHC genotype 1b patients.
T2  - Archives of Biological Sciences
T1  - RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin
VL  - 74
IS  - 1
SP  - 57
EP  - 66
DO  - 10.2298/ABS211208004K
ER  - 

@article{
author = "Kokanov, Nikola and Krajnović, Milena M. and Jovanović-Ćupić, Snežana P. and Kožik, Bojana and Petrović, Nina and Božović, Ana M. and Mandušić, Vesna",
year = "2022",
abstract = "Prevention of chronic hepatitis C (CHC) and its complications is based on antiviral therapy and early detection of reliable molecular markers in persons under risk. We investigated whether the methylation status of RASSF1A and p16 genes, alone or in combination with host and viral factors, affects the response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV). Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of the target promoter sequences of RASSF1A and p16 in circulating-free DNA from the peripheral blood of 49 patients with CHC genotype 1b. The methylation status of the examined genes did not affect the response to therapy. However, the simultaneous presence of either RASSF1A or p16 methylation and the CC genotype of IL28B was significantly related to a sustained virologic response (P=0.009 and P=0.032, respectively). After Bonferroni correction, only the result concerning the RASSF1A gene remained significant (P<0.0125). Methylation of RASSF1A was associated with the CC genotype of the IL28B gene (P=0.024) and a higher viral load (≥400 000 IU/mL, P=0.009). Our results suggest that combined analysis of RASSF1A gene methylation and IL28B rs12979860 polymorphism could potentially help in the prediction of therapy response in CHC genotype 1b patients.",
journal = "Archives of Biological Sciences",
title = "RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin",
volume = "74",
number = "1",
pages = "57-66",
doi = "10.2298/ABS211208004K"
}

Kokanov, N., Krajnović, M. M., Jovanović-Ćupić, S. P., Kožik, B., Petrović, N., Božović, A. M.,& Mandušić, V.. (2022). RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin. in Archives of Biological Sciences, 74(1), 57-66.
https://doi.org/10.2298/ABS211208004K

Kokanov N, Krajnović MM, Jovanović-Ćupić SP, Kožik B, Petrović N, Božović AM, Mandušić V. RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin. in Archives of Biological Sciences. 2022;74(1):57-66.
doi:10.2298/ABS211208004K .

Kokanov, Nikola, Krajnović, Milena M., Jovanović-Ćupić, Snežana P., Kožik, Bojana, Petrović, Nina, Božović, Ana M., Mandušić, Vesna, "RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin" in Archives of Biological Sciences, 74, no. 1 (2022):57-66,
https://doi.org/10.2298/ABS211208004K . .

TY  - JOUR
AU  - Kožik, Bojana
AU  - Krajnović, Milena M.
AU  - Kokanov, Nikola
AU  - Jovanović-Ćupić, Snežana P.
AU  - Božović, Ana M.
AU  - Todorović, Lidija
AU  - Mandušić, Vesna
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10354
AB  - Paper description:Patient responses to standard treatment of advanced stages of rectal carcinoma are variable, which emphasizes the need to define reliable predictive and prognostic molecular parameters.We propose a model of simultaneous analysis of KRAS gene mutation status and p16INK4a and p14ARF gene promoter methylation status in pre-treatment tumor biopsies.The simultaneous presence of p14ARF methylation and KRAS mutation was associated with more aggressive tumor behavior. The concurrent presence of alterations in all three examined genes was associated with shorter overall survival.Combined analysis of examined gene alterations revealed patient subgroups with a distinct pattern of tumor response and disease outcome.Abstract: Current management of locally advanced rectal carcinoma (LARC) involves preoperative chemoradiotherapy (preCRT) before surgery. Despite improved local control rate, the response to preCRT of individual patients is variable and may reflect heterogeneous biological properties among tumors of the same clinical stage. Identifying novel molecular parameters with predictive and/or prognostic value is of great clinical importance for a personalized therapeutic approach. In this study, KRAS mutation status was analyzed by direct sequencing, while methylation-specific polymerase chain reaction (MSP) was used to examine p16INK4a and p14ARF gene methylation status in pretreatment tumor biopsies of 60 patients with LARC. The examined molecular changes of KRAS, p16INK4a and p14ARF genes were mutually independent (p16INK4a/KRAS, P=0.272; p14ARF/KRAS, P=0.923; p16INK4a/p14ARF, P=0.715). However, the simultaneous presence of p14ARF methylation and KRAS mutation was associated with a more frequent appearance of local recurrences and distant metastasis (P=0.027). Moreover, patients with the simultaneous presence of p16INK4a and p14ARF methylation and KRAS mutation had significantly shorter overall survival (P=0.011). The obtained results strongly suggest that combined analyses of examined genetic and epigenetic molecular alterations could contribute to the identification of LARC patient subgroups with more aggressive tumor behavior and worse disease outcome.
T2  - Archives of Biological Sciences
T1  - Combined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy
VL  - 74
IS  - 2
SP  - 127
EP  - 134
DO  - 10.2298/ABS220222011K
ER  - 

@article{
author = "Kožik, Bojana and Krajnović, Milena M. and Kokanov, Nikola and Jovanović-Ćupić, Snežana P. and Božović, Ana M. and Todorović, Lidija and Mandušić, Vesna",
year = "2022",
abstract = "Paper description:Patient responses to standard treatment of advanced stages of rectal carcinoma are variable, which emphasizes the need to define reliable predictive and prognostic molecular parameters.We propose a model of simultaneous analysis of KRAS gene mutation status and p16INK4a and p14ARF gene promoter methylation status in pre-treatment tumor biopsies.The simultaneous presence of p14ARF methylation and KRAS mutation was associated with more aggressive tumor behavior. The concurrent presence of alterations in all three examined genes was associated with shorter overall survival.Combined analysis of examined gene alterations revealed patient subgroups with a distinct pattern of tumor response and disease outcome.Abstract: Current management of locally advanced rectal carcinoma (LARC) involves preoperative chemoradiotherapy (preCRT) before surgery. Despite improved local control rate, the response to preCRT of individual patients is variable and may reflect heterogeneous biological properties among tumors of the same clinical stage. Identifying novel molecular parameters with predictive and/or prognostic value is of great clinical importance for a personalized therapeutic approach. In this study, KRAS mutation status was analyzed by direct sequencing, while methylation-specific polymerase chain reaction (MSP) was used to examine p16INK4a and p14ARF gene methylation status in pretreatment tumor biopsies of 60 patients with LARC. The examined molecular changes of KRAS, p16INK4a and p14ARF genes were mutually independent (p16INK4a/KRAS, P=0.272; p14ARF/KRAS, P=0.923; p16INK4a/p14ARF, P=0.715). However, the simultaneous presence of p14ARF methylation and KRAS mutation was associated with a more frequent appearance of local recurrences and distant metastasis (P=0.027). Moreover, patients with the simultaneous presence of p16INK4a and p14ARF methylation and KRAS mutation had significantly shorter overall survival (P=0.011). The obtained results strongly suggest that combined analyses of examined genetic and epigenetic molecular alterations could contribute to the identification of LARC patient subgroups with more aggressive tumor behavior and worse disease outcome.",
journal = "Archives of Biological Sciences",
title = "Combined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy",
volume = "74",
number = "2",
pages = "127-134",
doi = "10.2298/ABS220222011K"
}

Kožik, B., Krajnović, M. M., Kokanov, N., Jovanović-Ćupić, S. P., Božović, A. M., Todorović, L.,& Mandušić, V.. (2022). Combined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy. in Archives of Biological Sciences, 74(2), 127-134.
https://doi.org/10.2298/ABS220222011K

Kožik B, Krajnović MM, Kokanov N, Jovanović-Ćupić SP, Božović AM, Todorović L, Mandušić V. Combined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy. in Archives of Biological Sciences. 2022;74(2):127-134.
doi:10.2298/ABS220222011K .

Kožik, Bojana, Krajnović, Milena M., Kokanov, Nikola, Jovanović-Ćupić, Snežana P., Božović, Ana M., Todorović, Lidija, Mandušić, Vesna, "Combined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy" in Archives of Biological Sciences, 74, no. 2 (2022):127-134,
https://doi.org/10.2298/ABS220222011K . .

TY  - CONF
AU  - Kožik, Bojana
AU  - Božović, Ana
AU  - Kokanov, Nikola
AU  - Mandušić, Vesna
AU  - Živaljević, Vladan
AU  - Paunović, Ivan
AU  - Stanojević, Boban
AU  - Todorović, Lidija
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12507
AB  - Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Identifying novel molecular parameters with prognostic value is of great clinical importance for a personalized therapeutic approach. Epigenetic changes have been proven to play an important role in cancer pathogenesis. Hypermethylation of the promoter region of p16INK4a gene has been shown to be a significant event in a number of cancer types. Several studies suggested that it might have a prognostic impact in ACC as well, however the data are relatively ambiguous.  According to the dataset from The Cancer Genome Atlas (TCGA) database, in cohort of 79 ACC patients, the analysis of the p16INK4a gene methylation showed that higher methylation was associated with shorter progression-free and overall survival. We evaluate the methylation status of p16INK4a in a preliminary cohort of 30 ACC patients by using the methylation-specific polymerase chain reaction (MSP) and aberrant methylation of p16INK4a was present in 66.7% (20/30) of cases. Our results indicate that epigenetic alteration of this gene is common event in ACC and may be important for pathogenesis of this tumor type. Although, we did not observed significant association between p16INK4a methylation status and clinico-pathological characteristics (age and gender, tumor size and weight, regional lymph node and distant metastasis), we will evaluate methylation status of this gene in another 30 ACC cases and compare it with methylation profile of adrenocortical adenoma patients, since inactivation of p16INK4a gene by promoter hypermethylation has been frequently reported as an early event in premalignant lesions in many tumor types.
PB  - Poland : The National Institute of Cardiology
C3  - The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts
T1  - Methylation status of p16INK4a tumor-suppressor gene in adrenocortical carcinoma: preliminary study
SP  - A17
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12507
ER  - 

@conference{
author = "Kožik, Bojana and Božović, Ana and Kokanov, Nikola and Mandušić, Vesna and Živaljević, Vladan and Paunović, Ivan and Stanojević, Boban and Todorović, Lidija",
year = "2022",
abstract = "Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Identifying novel molecular parameters with prognostic value is of great clinical importance for a personalized therapeutic approach. Epigenetic changes have been proven to play an important role in cancer pathogenesis. Hypermethylation of the promoter region of p16INK4a gene has been shown to be a significant event in a number of cancer types. Several studies suggested that it might have a prognostic impact in ACC as well, however the data are relatively ambiguous.  According to the dataset from The Cancer Genome Atlas (TCGA) database, in cohort of 79 ACC patients, the analysis of the p16INK4a gene methylation showed that higher methylation was associated with shorter progression-free and overall survival. We evaluate the methylation status of p16INK4a in a preliminary cohort of 30 ACC patients by using the methylation-specific polymerase chain reaction (MSP) and aberrant methylation of p16INK4a was present in 66.7% (20/30) of cases. Our results indicate that epigenetic alteration of this gene is common event in ACC and may be important for pathogenesis of this tumor type. Although, we did not observed significant association between p16INK4a methylation status and clinico-pathological characteristics (age and gender, tumor size and weight, regional lymph node and distant metastasis), we will evaluate methylation status of this gene in another 30 ACC cases and compare it with methylation profile of adrenocortical adenoma patients, since inactivation of p16INK4a gene by promoter hypermethylation has been frequently reported as an early event in premalignant lesions in many tumor types.",
publisher = "Poland : The National Institute of Cardiology",
journal = "The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts",
title = "Methylation status of p16INK4a tumor-suppressor gene in adrenocortical carcinoma: preliminary study",
pages = "A17",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12507"
}

Kožik, B., Božović, A., Kokanov, N., Mandušić, V., Živaljević, V., Paunović, I., Stanojević, B.,& Todorović, L.. (2022). Methylation status of p16INK4a tumor-suppressor gene in adrenocortical carcinoma: preliminary study. in The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts
Poland : The National Institute of Cardiology., A17.
https://hdl.handle.net/21.15107/rcub_vinar_12507

Kožik B, Božović A, Kokanov N, Mandušić V, Živaljević V, Paunović I, Stanojević B, Todorović L. Methylation status of p16INK4a tumor-suppressor gene in adrenocortical carcinoma: preliminary study. in The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts. 2022;:A17.
https://hdl.handle.net/21.15107/rcub_vinar_12507 .

Kožik, Bojana, Božović, Ana, Kokanov, Nikola, Mandušić, Vesna, Živaljević, Vladan, Paunović, Ivan, Stanojević, Boban, Todorović, Lidija, "Methylation status of p16INK4a tumor-suppressor gene in adrenocortical carcinoma: preliminary study" in The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts (2022):A17,
https://hdl.handle.net/21.15107/rcub_vinar_12507 .

TY  - CONF
AU  - Todorović, Lidija
AU  - Kožik, Bojana
AU  - Božović, Ana
AU  - Mandušić, Vesna
AU  - Stanojević, Boban
AU  - Živaljević, Vladan
AU  - Paunović, Ivan
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12509
AB  - Adrenocortical tumors (ACTs) are heterogeneous neoplasms with incompletely understood pathogenesis. Correct differential diagnosis between adrenocortical adenoma (ACA) and localized adrenocortical carcinoma (ACC), as well as improved prognostic stratification of ACC patients, are of great clinical importance. Alterations in gene expression patterns have been found in adrenocortical neoplasms compared to normal tissue. In addition to having a role in tumorigenesis, distinct gene expression signatures may help to distinguish different ACT types. The combined expression patterns of PINK1, DLGAP5 and BUB1B have been suggested as malignancy and outcome predictors in previous studies. In order to validate their diagnostic/prognostic potential, we investigated the expression levels of these three genes and their association with clinico-pathological parameters in a cohort of 47 ACC and 15 ACA patients from Serbia. In addition, we analyzed the association of their expression levels with survival data in an independent ACC cohort of 79 patients from The Cancer Genome Atlas (TCGA) database. The results showed that high expression levels of BUB1B and DLGAP5, and low expression levels of PINK1 significantly associated with ACC. Moreover, combined expression of both DLGAP5 and BUB1B with PINK1 were significantly higher in localized ACC compared with ACA. The results from the TCGA cohort showed that expression alterations of these genes were strong predictors of disease-free and overall survival in ACC patients. These results are consistent with the previously reported results and confirm that the expression patterns of PINK1, DLGAP5 and BUB1B might have value as molecular predictors of malignancy and/or survival in ACC patients.
PB  - Poland : The National Institute of Cardiology
C3  - The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts
T1  - Validation of diagnostic and prognostic potential of PINK1, DLGAP5 and BUB1B expression patterns in adrenocortical tumors
SP  - A39
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12509
ER  - 

@conference{
author = "Todorović, Lidija and Kožik, Bojana and Božović, Ana and Mandušić, Vesna and Stanojević, Boban and Živaljević, Vladan and Paunović, Ivan",
year = "2022",
abstract = "Adrenocortical tumors (ACTs) are heterogeneous neoplasms with incompletely understood pathogenesis. Correct differential diagnosis between adrenocortical adenoma (ACA) and localized adrenocortical carcinoma (ACC), as well as improved prognostic stratification of ACC patients, are of great clinical importance. Alterations in gene expression patterns have been found in adrenocortical neoplasms compared to normal tissue. In addition to having a role in tumorigenesis, distinct gene expression signatures may help to distinguish different ACT types. The combined expression patterns of PINK1, DLGAP5 and BUB1B have been suggested as malignancy and outcome predictors in previous studies. In order to validate their diagnostic/prognostic potential, we investigated the expression levels of these three genes and their association with clinico-pathological parameters in a cohort of 47 ACC and 15 ACA patients from Serbia. In addition, we analyzed the association of their expression levels with survival data in an independent ACC cohort of 79 patients from The Cancer Genome Atlas (TCGA) database. The results showed that high expression levels of BUB1B and DLGAP5, and low expression levels of PINK1 significantly associated with ACC. Moreover, combined expression of both DLGAP5 and BUB1B with PINK1 were significantly higher in localized ACC compared with ACA. The results from the TCGA cohort showed that expression alterations of these genes were strong predictors of disease-free and overall survival in ACC patients. These results are consistent with the previously reported results and confirm that the expression patterns of PINK1, DLGAP5 and BUB1B might have value as molecular predictors of malignancy and/or survival in ACC patients.",
publisher = "Poland : The National Institute of Cardiology",
journal = "The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts",
title = "Validation of diagnostic and prognostic potential of PINK1, DLGAP5 and BUB1B expression patterns in adrenocortical tumors",
pages = "A39",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12509"
}

Todorović, L., Kožik, B., Božović, A., Mandušić, V., Stanojević, B., Živaljević, V.,& Paunović, I.. (2022). Validation of diagnostic and prognostic potential of PINK1, DLGAP5 and BUB1B expression patterns in adrenocortical tumors. in The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts
Poland : The National Institute of Cardiology., A39.
https://hdl.handle.net/21.15107/rcub_vinar_12509

Todorović L, Kožik B, Božović A, Mandušić V, Stanojević B, Živaljević V, Paunović I. Validation of diagnostic and prognostic potential of PINK1, DLGAP5 and BUB1B expression patterns in adrenocortical tumors. in The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts. 2022;:A39.
https://hdl.handle.net/21.15107/rcub_vinar_12509 .

Todorović, Lidija, Kožik, Bojana, Božović, Ana, Mandušić, Vesna, Stanojević, Boban, Živaljević, Vladan, Paunović, Ivan, "Validation of diagnostic and prognostic potential of PINK1, DLGAP5 and BUB1B expression patterns in adrenocortical tumors" in The 21st ENS@T and 1st COST-HARMONIS@TION meeting : Book of abstracts (2022):A39,
https://hdl.handle.net/21.15107/rcub_vinar_12509 .

TY  - CONF
AU  - Kožik, Bojana
AU  - Krajnović, Milena
AU  - Jovanović Ćupić, Snežana
AU  - Kokanov, Nikola
AU  - Božović, Ana
AU  - Todorović, Lidija
AU  - Mandušić, Vesna
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12647
AB  - Background: Rectal cancer represents approximately 30% of cases of colorectal carcinoma and locally advanced stages of rectal cancers (LARC) remain a great clinical challenge due to chemoresistance and high local recurrence rate. The current management of LARC involves neoadjuvant chemoradiotherapy (neoCRT) before surgery. Since only a subset of patients benefit from this preoperative treatment, the development of reliable molecular biomarkers is required. In this retrospective study, we investigated the mutation status of K-ras proto-oncogene, as well as the expression level of apoptosis regulator protein, BCL2, to evaluate their potential predictive role in LARC. Patients and Methods: K-ras gene mutation status was determined by direct sequencing, while BCL2 protein expression was detected immunohistochemically (semi-quantitatively method) in pre-therapeutic and pre-operative biopsy specimens of 61 patients with LARC treated with neoCRT. Results: According to the results of this study, K-ras mutation status and BCL2 expression status were mutually independent events. In general, K-ras mutation status did not affect the response to CRT, while in the group of patients with high BCL2 expression was observed a tendency toward a worse response to the same treatment (p=0.098). However, the subgroup of patients with the simultaneous presence of K-ras mutation and high BCL2 expression showed significantly worse response to neoCRT (p=0.022). Conclusion: Obtained results strongly suggest that combined analyses of molecular aberrations in K-ras proto-oncogene and BCL2 anti-apoptotic protein expression level could have a potential predictive role and important clinical relevance in the identification of LARC patient subgroups, with a distinct pattern of response to neoCRT.
PB  - Belgrade : Serbian Association for Cancer Research (SDIR)
C3  - SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts
T1  - Potential predictive role of K-ras gene mutation and BCL2 protein expression status in locally advanced rectal cancers treated with neoadjuvant chemoradiotherapy
SP  - 20
EP  - 20
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12647
ER  - 

@conference{
author = "Kožik, Bojana and Krajnović, Milena and Jovanović Ćupić, Snežana and Kokanov, Nikola and Božović, Ana and Todorović, Lidija and Mandušić, Vesna",
year = "2021",
abstract = "Background: Rectal cancer represents approximately 30% of cases of colorectal carcinoma and locally advanced stages of rectal cancers (LARC) remain a great clinical challenge due to chemoresistance and high local recurrence rate. The current management of LARC involves neoadjuvant chemoradiotherapy (neoCRT) before surgery. Since only a subset of patients benefit from this preoperative treatment, the development of reliable molecular biomarkers is required. In this retrospective study, we investigated the mutation status of K-ras proto-oncogene, as well as the expression level of apoptosis regulator protein, BCL2, to evaluate their potential predictive role in LARC. Patients and Methods: K-ras gene mutation status was determined by direct sequencing, while BCL2 protein expression was detected immunohistochemically (semi-quantitatively method) in pre-therapeutic and pre-operative biopsy specimens of 61 patients with LARC treated with neoCRT. Results: According to the results of this study, K-ras mutation status and BCL2 expression status were mutually independent events. In general, K-ras mutation status did not affect the response to CRT, while in the group of patients with high BCL2 expression was observed a tendency toward a worse response to the same treatment (p=0.098). However, the subgroup of patients with the simultaneous presence of K-ras mutation and high BCL2 expression showed significantly worse response to neoCRT (p=0.022). Conclusion: Obtained results strongly suggest that combined analyses of molecular aberrations in K-ras proto-oncogene and BCL2 anti-apoptotic protein expression level could have a potential predictive role and important clinical relevance in the identification of LARC patient subgroups, with a distinct pattern of response to neoCRT.",
publisher = "Belgrade : Serbian Association for Cancer Research (SDIR)",
journal = "SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts",
title = "Potential predictive role of K-ras gene mutation and BCL2 protein expression status in locally advanced rectal cancers treated with neoadjuvant chemoradiotherapy",
pages = "20-20",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12647"
}

Kožik, B., Krajnović, M., Jovanović Ćupić, S., Kokanov, N., Božović, A., Todorović, L.,& Mandušić, V.. (2021). Potential predictive role of K-ras gene mutation and BCL2 protein expression status in locally advanced rectal cancers treated with neoadjuvant chemoradiotherapy. in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts
Belgrade : Serbian Association for Cancer Research (SDIR)., 20-20.
https://hdl.handle.net/21.15107/rcub_vinar_12647

Kožik B, Krajnović M, Jovanović Ćupić S, Kokanov N, Božović A, Todorović L, Mandušić V. Potential predictive role of K-ras gene mutation and BCL2 protein expression status in locally advanced rectal cancers treated with neoadjuvant chemoradiotherapy. in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts. 2021;:20-20.
https://hdl.handle.net/21.15107/rcub_vinar_12647 .

Kožik, Bojana, Krajnović, Milena, Jovanović Ćupić, Snežana, Kokanov, Nikola, Božović, Ana, Todorović, Lidija, Mandušić, Vesna, "Potential predictive role of K-ras gene mutation and BCL2 protein expression status in locally advanced rectal cancers treated with neoadjuvant chemoradiotherapy" in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts (2021):20-20,
https://hdl.handle.net/21.15107/rcub_vinar_12647 .

TY  - CONF
AU  - Todorović, Lidija
AU  - Stanojević, Boban
AU  - Kožik, Bojana
AU  - Božović, Ana
AU  - Mandušić, Vesna
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12510
AB  - Background: A number of studies point to a significant role of microRNAs (miRNAs) in papillary thyroid cancer (PTC), where specific miRNA expression profiles associate with distinct clinical and biological phenotypes of the lesion. One of the microRNAs deregulated in PTC is miR-30a-3p. Evidence suggests that estrogen receptor β (ERβ), also found to be deregulated in PTCs, may directly regulate microRNA-30a-3p biogenesis and expression. Considering the possibility that ERβ might influence PTC cell behavior via miRNAs, in particular, miR-30a-3p, we have investigated their expression and correlation in PTCs with different clinico-pathological characteristics. Patients and Methods: Quantitative PCR was used to determine the relative miR-30a-3p and ERβ expression levels in 37 pairs of PTCs and matched non-tumor thyroid tissues. Results: The expression levels of miR-30a and ERβ were significantly altered in tumors compared with non-tumor tissues. A negative correlation between miR-30 and ERβ was detected in tumors with pT4 category (P=0.038, r = - 0.738) and capsular invasion (only in women) (P=0.041. r= -0.552) compared to positive correlations (or trends) found in tumors with lower pT categories (pT1+pT2) (P=0.061, r=0.463) and tumors with no capsular invasion (P=0.019, r=0.618). Similar trend was found in tumors with classic papillary pattern in the group of women (P=0.09, r= - 0.432) while in women with histovariants other than classic there was a trend towards positive correlation (P=0.066, r=0.486). Conclusion: The results suggest that in some PTCs, ERβ might negatively regulate miR-30a expression, and the opposite roles they may play are associated with more aggressive tumor features.
PB  - Belgrade : Serbian Association for Cancer Research (SDIR)
C3  - SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts
T1  - The expression of microRNA-30a-3p and estrogen receptor β in papillary thyroid cancer
SP  - 42
EP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12510
ER  - 

@conference{
author = "Todorović, Lidija and Stanojević, Boban and Kožik, Bojana and Božović, Ana and Mandušić, Vesna",
year = "2021",
abstract = "Background: A number of studies point to a significant role of microRNAs (miRNAs) in papillary thyroid cancer (PTC), where specific miRNA expression profiles associate with distinct clinical and biological phenotypes of the lesion. One of the microRNAs deregulated in PTC is miR-30a-3p. Evidence suggests that estrogen receptor β (ERβ), also found to be deregulated in PTCs, may directly regulate microRNA-30a-3p biogenesis and expression. Considering the possibility that ERβ might influence PTC cell behavior via miRNAs, in particular, miR-30a-3p, we have investigated their expression and correlation in PTCs with different clinico-pathological characteristics. Patients and Methods: Quantitative PCR was used to determine the relative miR-30a-3p and ERβ expression levels in 37 pairs of PTCs and matched non-tumor thyroid tissues. Results: The expression levels of miR-30a and ERβ were significantly altered in tumors compared with non-tumor tissues. A negative correlation between miR-30 and ERβ was detected in tumors with pT4 category (P=0.038, r = - 0.738) and capsular invasion (only in women) (P=0.041. r= -0.552) compared to positive correlations (or trends) found in tumors with lower pT categories (pT1+pT2) (P=0.061, r=0.463) and tumors with no capsular invasion (P=0.019, r=0.618). Similar trend was found in tumors with classic papillary pattern in the group of women (P=0.09, r= - 0.432) while in women with histovariants other than classic there was a trend towards positive correlation (P=0.066, r=0.486). Conclusion: The results suggest that in some PTCs, ERβ might negatively regulate miR-30a expression, and the opposite roles they may play are associated with more aggressive tumor features.",
publisher = "Belgrade : Serbian Association for Cancer Research (SDIR)",
journal = "SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts",
title = "The expression of microRNA-30a-3p and estrogen receptor β in papillary thyroid cancer",
pages = "42-42",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12510"
}

Todorović, L., Stanojević, B., Kožik, B., Božović, A.,& Mandušić, V.. (2021). The expression of microRNA-30a-3p and estrogen receptor β in papillary thyroid cancer. in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts
Belgrade : Serbian Association for Cancer Research (SDIR)., 42-42.
https://hdl.handle.net/21.15107/rcub_vinar_12510

Todorović L, Stanojević B, Kožik B, Božović A, Mandušić V. The expression of microRNA-30a-3p and estrogen receptor β in papillary thyroid cancer. in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts. 2021;:42-42.
https://hdl.handle.net/21.15107/rcub_vinar_12510 .

Todorović, Lidija, Stanojević, Boban, Kožik, Bojana, Božović, Ana, Mandušić, Vesna, "The expression of microRNA-30a-3p and estrogen receptor β in papillary thyroid cancer" in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts (2021):42-42,
https://hdl.handle.net/21.15107/rcub_vinar_12510 .

TY  - JOUR
AU  - Todorović, Lidija
AU  - Stamenković, Gorana
AU  - Vučetić-Tadić, Biljana
AU  - Umezawa, Kazuo
AU  - Božović, Ana M.
AU  - Yamashita, Shunichi
AU  - Stanojević, Boban
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9413
AB  - The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.
T2  - Archives of Biological Sciences
T1  - Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2
VL  - 73
IS  - 1
SP  - 31
EP  - 38
DO  - 10.2298/ABS201010055T
ER  - 

@article{
author = "Todorović, Lidija and Stamenković, Gorana and Vučetić-Tadić, Biljana and Umezawa, Kazuo and Božović, Ana M. and Yamashita, Shunichi and Stanojević, Boban",
year = "2021",
abstract = "The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.",
journal = "Archives of Biological Sciences",
title = "Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2",
volume = "73",
number = "1",
pages = "31-38",
doi = "10.2298/ABS201010055T"
}

Todorović, L., Stamenković, G., Vučetić-Tadić, B., Umezawa, K., Božović, A. M., Yamashita, S.,& Stanojević, B.. (2021). Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2. in Archives of Biological Sciences, 73(1), 31-38.
https://doi.org/10.2298/ABS201010055T

Todorović L, Stamenković G, Vučetić-Tadić B, Umezawa K, Božović AM, Yamashita S, Stanojević B. Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2. in Archives of Biological Sciences. 2021;73(1):31-38.
doi:10.2298/ABS201010055T .

Todorović, Lidija, Stamenković, Gorana, Vučetić-Tadić, Biljana, Umezawa, Kazuo, Božović, Ana M., Yamashita, Shunichi, Stanojević, Boban, "Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2" in Archives of Biological Sciences, 73, no. 1 (2021):31-38,
https://doi.org/10.2298/ABS201010055T . .

TY  - JOUR
AU  - Božović, Ana M.
AU  - Mandušić, Vesna
AU  - Todorović, Lidija
AU  - Krajnović, Milena M.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9560
AB  - The discovery of the Estrogen Receptor Beta (ERβ) in 1996 opened new perspectives in the diagnostics and therapy of different types of cancer. Here, we present a review of the present research knowledge about its role in endocrine-related cancers: breast, prostate, and thyroid, and colorectal cancers. We also discuss the reasons for the controversy of its role in carcinogenesis and why it is still not in use as a biomarker in clinical practice. Given that the diagnostics and therapy would benefit from the introduction of new biomarkers, we suggest ways to overcome the contradictions in elucidating the role of ERβ.
T2  - International Journal of Molecular Sciences
T1  - Estrogen Receptor Beta: The Promising Biomarker and Potential Target in Metastases
VL  - 22
IS  - 4
SP  - 1656
DO  - 10.3390/ijms22041656
ER  - 

@article{
author = "Božović, Ana M. and Mandušić, Vesna and Todorović, Lidija and Krajnović, Milena M.",
year = "2021",
abstract = "The discovery of the Estrogen Receptor Beta (ERβ) in 1996 opened new perspectives in the diagnostics and therapy of different types of cancer. Here, we present a review of the present research knowledge about its role in endocrine-related cancers: breast, prostate, and thyroid, and colorectal cancers. We also discuss the reasons for the controversy of its role in carcinogenesis and why it is still not in use as a biomarker in clinical practice. Given that the diagnostics and therapy would benefit from the introduction of new biomarkers, we suggest ways to overcome the contradictions in elucidating the role of ERβ.",
journal = "International Journal of Molecular Sciences",
title = "Estrogen Receptor Beta: The Promising Biomarker and Potential Target in Metastases",
volume = "22",
number = "4",
pages = "1656",
doi = "10.3390/ijms22041656"
}

Božović, A. M., Mandušić, V., Todorović, L.,& Krajnović, M. M.. (2021). Estrogen Receptor Beta: The Promising Biomarker and Potential Target in Metastases. in International Journal of Molecular Sciences, 22(4), 1656.
https://doi.org/10.3390/ijms22041656

Božović AM, Mandušić V, Todorović L, Krajnović MM. Estrogen Receptor Beta: The Promising Biomarker and Potential Target in Metastases. in International Journal of Molecular Sciences. 2021;22(4):1656.
doi:10.3390/ijms22041656 .

Božović, Ana M., Mandušić, Vesna, Todorović, Lidija, Krajnović, Milena M., "Estrogen Receptor Beta: The Promising Biomarker and Potential Target in Metastases" in International Journal of Molecular Sciences, 22, no. 4 (2021):1656,
https://doi.org/10.3390/ijms22041656 . .

TY  - CONF
AU  - Radulović, Olga
AU  - Jovanović-Ćupić, Snežana
AU  - Krajnović, Milena
AU  - Božović, Ana
AU  - Marković, Bojana
AU  - Kokanov, Nikola
AU  - Petrović, Nina
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12452
C3  - 1st Belgrade International Molecular Life Science Conference for Students : Abstract book & Program
T1  - IDC-DCIS high-miR-21/Her-2 positive and pure IDC high-miR-21/ER+/PR+ tumors might have therapeutically challenging phenotypes for future anti-miR-21 therapy
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12452
ER  - 

@conference{
author = "Radulović, Olga and Jovanović-Ćupić, Snežana and Krajnović, Milena and Božović, Ana and Marković, Bojana and Kokanov, Nikola and Petrović, Nina",
year = "2015",
journal = "1st Belgrade International Molecular Life Science Conference for Students : Abstract book & Program",
title = "IDC-DCIS high-miR-21/Her-2 positive and pure IDC high-miR-21/ER+/PR+ tumors might have therapeutically challenging phenotypes for future anti-miR-21 therapy",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12452"
}

Radulović, O., Jovanović-Ćupić, S., Krajnović, M., Božović, A., Marković, B., Kokanov, N.,& Petrović, N.. (2015). IDC-DCIS high-miR-21/Her-2 positive and pure IDC high-miR-21/ER+/PR+ tumors might have therapeutically challenging phenotypes for future anti-miR-21 therapy. in 1st Belgrade International Molecular Life Science Conference for Students : Abstract book & Program.
https://hdl.handle.net/21.15107/rcub_vinar_12452

Radulović O, Jovanović-Ćupić S, Krajnović M, Božović A, Marković B, Kokanov N, Petrović N. IDC-DCIS high-miR-21/Her-2 positive and pure IDC high-miR-21/ER+/PR+ tumors might have therapeutically challenging phenotypes for future anti-miR-21 therapy. in 1st Belgrade International Molecular Life Science Conference for Students : Abstract book & Program. 2015;.
https://hdl.handle.net/21.15107/rcub_vinar_12452 .

Radulović, Olga, Jovanović-Ćupić, Snežana, Krajnović, Milena, Božović, Ana, Marković, Bojana, Kokanov, Nikola, Petrović, Nina, "IDC-DCIS high-miR-21/Her-2 positive and pure IDC high-miR-21/ER+/PR+ tumors might have therapeutically challenging phenotypes for future anti-miR-21 therapy" in 1st Belgrade International Molecular Life Science Conference for Students : Abstract book & Program (2015),
https://hdl.handle.net/21.15107/rcub_vinar_12452 .

TY  - JOUR
AU  - Bajić, Vladan P.
AU  - Mandušić, Vesna
AU  - Stefanova, Elka
AU  - Božović, Ana M.
AU  - Davidović, Radoslav S.
AU  - Živković, Lada
AU  - Čabarkapa, Andrea
AU  - Spremo-Potparević, Biljana
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/314
AB  - X-chromosome instability has been a long established feature in Alzheimers disease ( AD). Premature centromere division and aneuploidy of the X-chromosome has been found in peripheral blood lymphocytes and neuronal tissue in female AD patients. Interestingly, only one chromosome of the X pair has been affected. These results raised a question, Is the X-chromosome inactivation pattern altered in peripheral blood lymphocytes ofwomen affected by AD? To address this question, we analyzed the methylation status of androgen receptor promoter which may show us any deviation from the 50 : 50% X inactivation status in peripheral blood lymphocytes ofwomen with AD. Our results showed skewed inactivation patterns ( GT 90%). These findings suggest that an epigenetic alteration on the inactivation centers of the X-chromosome (or skewing) relates not only to aging, by might be a novel property that could account for the higher incidence of AD in women.
T2  - Journal of Alzheimers Disease
T1  - Skewed X-Chromosome Inactivation in Women Affected by Alzheimers Disease
VL  - 43
IS  - 4
SP  - 1251
EP  - 1259
DO  - 10.3233/JAD-141674
ER  - 

@article{
author = "Bajić, Vladan P. and Mandušić, Vesna and Stefanova, Elka and Božović, Ana M. and Davidović, Radoslav S. and Živković, Lada and Čabarkapa, Andrea and Spremo-Potparević, Biljana",
year = "2015",
abstract = "X-chromosome instability has been a long established feature in Alzheimers disease ( AD). Premature centromere division and aneuploidy of the X-chromosome has been found in peripheral blood lymphocytes and neuronal tissue in female AD patients. Interestingly, only one chromosome of the X pair has been affected. These results raised a question, Is the X-chromosome inactivation pattern altered in peripheral blood lymphocytes ofwomen affected by AD? To address this question, we analyzed the methylation status of androgen receptor promoter which may show us any deviation from the 50 : 50% X inactivation status in peripheral blood lymphocytes ofwomen with AD. Our results showed skewed inactivation patterns ( GT 90%). These findings suggest that an epigenetic alteration on the inactivation centers of the X-chromosome (or skewing) relates not only to aging, by might be a novel property that could account for the higher incidence of AD in women.",
journal = "Journal of Alzheimers Disease",
title = "Skewed X-Chromosome Inactivation in Women Affected by Alzheimers Disease",
volume = "43",
number = "4",
pages = "1251-1259",
doi = "10.3233/JAD-141674"
}

Bajić, V. P., Mandušić, V., Stefanova, E., Božović, A. M., Davidović, R. S., Živković, L., Čabarkapa, A.,& Spremo-Potparević, B.. (2015). Skewed X-Chromosome Inactivation in Women Affected by Alzheimers Disease. in Journal of Alzheimers Disease, 43(4), 1251-1259.
https://doi.org/10.3233/JAD-141674

Bajić VP, Mandušić V, Stefanova E, Božović AM, Davidović RS, Živković L, Čabarkapa A, Spremo-Potparević B. Skewed X-Chromosome Inactivation in Women Affected by Alzheimers Disease. in Journal of Alzheimers Disease. 2015;43(4):1251-1259.
doi:10.3233/JAD-141674 .

Bajić, Vladan P., Mandušić, Vesna, Stefanova, Elka, Božović, Ana M., Davidović, Radoslav S., Živković, Lada, Čabarkapa, Andrea, Spremo-Potparević, Biljana, "Skewed X-Chromosome Inactivation in Women Affected by Alzheimers Disease" in Journal of Alzheimers Disease, 43, no. 4 (2015):1251-1259,
https://doi.org/10.3233/JAD-141674 . .

TY  - JOUR
AU  - Jovanović-Ćupić, Snežana P.
AU  - Glišić, Sanja
AU  - Stanojevic, M.
AU  - Vasiljević, N.
AU  - Bojić, Tijana
AU  - Božović, Ana M.
AU  - Dimitrijević, Bogomir B.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5858
AB  - Hepatitis C virus infection is the most common chronic blood-borne infection and one of the most important causes of chronic liver disease. Knowing the predictors associated with pegylated interferon/ribavirin (PEG-IFN/RBV) combination therapy response is important for evidence-based treatment recommendations. The goal of this study was to identify host and viral factors of response to PEG-IFN/RBV treatment in chronic hepatitis C genotype 1b patients. We have examined the relationship between gender, age, level of alanine aminotransferase (ALT), viral load and liver fibrosis progression on therapy response. ALT level and viral load were evaluated before starting treatment with combination therapy. The elevated levels of ALT and route of HCV transmission were found to be significantly associated with the response to therapy in HCV-infected patients. Our findings may be useful for estimating a patients likelihood Of achieving sustained viral response.
T2  - Archives of Biological Sciences
T1  - Response Factors to Pegylated Interferon-Alfa/Ribavirin Treatment in Chronic Hepatitis C Patients Genotype 1b
VL  - 66
IS  - 1
SP  - 193
EP  - 201
DO  - 10.2298/ABS1401193J
ER  - 

@article{
author = "Jovanović-Ćupić, Snežana P. and Glišić, Sanja and Stanojevic, M. and Vasiljević, N. and Bojić, Tijana and Božović, Ana M. and Dimitrijević, Bogomir B.",
year = "2014",
abstract = "Hepatitis C virus infection is the most common chronic blood-borne infection and one of the most important causes of chronic liver disease. Knowing the predictors associated with pegylated interferon/ribavirin (PEG-IFN/RBV) combination therapy response is important for evidence-based treatment recommendations. The goal of this study was to identify host and viral factors of response to PEG-IFN/RBV treatment in chronic hepatitis C genotype 1b patients. We have examined the relationship between gender, age, level of alanine aminotransferase (ALT), viral load and liver fibrosis progression on therapy response. ALT level and viral load were evaluated before starting treatment with combination therapy. The elevated levels of ALT and route of HCV transmission were found to be significantly associated with the response to therapy in HCV-infected patients. Our findings may be useful for estimating a patients likelihood Of achieving sustained viral response.",
journal = "Archives of Biological Sciences",
title = "Response Factors to Pegylated Interferon-Alfa/Ribavirin Treatment in Chronic Hepatitis C Patients Genotype 1b",
volume = "66",
number = "1",
pages = "193-201",
doi = "10.2298/ABS1401193J"
}

Jovanović-Ćupić, S. P., Glišić, S., Stanojevic, M., Vasiljević, N., Bojić, T., Božović, A. M.,& Dimitrijević, B. B.. (2014). Response Factors to Pegylated Interferon-Alfa/Ribavirin Treatment in Chronic Hepatitis C Patients Genotype 1b. in Archives of Biological Sciences, 66(1), 193-201.
https://doi.org/10.2298/ABS1401193J

Jovanović-Ćupić SP, Glišić S, Stanojevic M, Vasiljević N, Bojić T, Božović AM, Dimitrijević BB. Response Factors to Pegylated Interferon-Alfa/Ribavirin Treatment in Chronic Hepatitis C Patients Genotype 1b. in Archives of Biological Sciences. 2014;66(1):193-201.
doi:10.2298/ABS1401193J .

Jovanović-Ćupić, Snežana P., Glišić, Sanja, Stanojevic, M., Vasiljević, N., Bojić, Tijana, Božović, Ana M., Dimitrijević, Bogomir B., "Response Factors to Pegylated Interferon-Alfa/Ribavirin Treatment in Chronic Hepatitis C Patients Genotype 1b" in Archives of Biological Sciences, 66, no. 1 (2014):193-201,
https://doi.org/10.2298/ABS1401193J . .

TY  - JOUR
AU  - Davidović, Radoslav S.
AU  - Božović, Ana M.
AU  - Mandušić, Vesna
AU  - Krajnović, Milena M.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/74
AB  - Methylation-specific PCR (MSP) is still the method of choice for a single gene methylation study. The proper design of the primer pairs is a prerequisite for obtaining reliable PCR results. Despite numerous protocols describing the rules for MSP primer design, none of them provide a comprehensive approach to the problem. Our aim was to depict a workflow for the primer design that is concise and easy to follow. In order to achieve this goal, adequate tools for promoter sequence retrieval, MSP primer design and subsequent in silico analysis are presented and discussed. Furthermore, a few instructive examples regarding a good versus a poor primer design are provided. Finally, primer design is demonstrated according to the proposed workflow. This article aims to provide researchers, interested in a single gene methylation studies, with useful information regarding successful primer design.
T2  - Central European Journal of Biology
T1  - Methylation-specific PCR: four steps in primer design
VL  - 9
IS  - 12
SP  - 1127
EP  - 1139
DO  - 10.2478/s11535-014-0324-z
ER  - 

@article{
author = "Davidović, Radoslav S. and Božović, Ana M. and Mandušić, Vesna and Krajnović, Milena M.",
year = "2014",
abstract = "Methylation-specific PCR (MSP) is still the method of choice for a single gene methylation study. The proper design of the primer pairs is a prerequisite for obtaining reliable PCR results. Despite numerous protocols describing the rules for MSP primer design, none of them provide a comprehensive approach to the problem. Our aim was to depict a workflow for the primer design that is concise and easy to follow. In order to achieve this goal, adequate tools for promoter sequence retrieval, MSP primer design and subsequent in silico analysis are presented and discussed. Furthermore, a few instructive examples regarding a good versus a poor primer design are provided. Finally, primer design is demonstrated according to the proposed workflow. This article aims to provide researchers, interested in a single gene methylation studies, with useful information regarding successful primer design.",
journal = "Central European Journal of Biology",
title = "Methylation-specific PCR: four steps in primer design",
volume = "9",
number = "12",
pages = "1127-1139",
doi = "10.2478/s11535-014-0324-z"
}

Davidović, R. S., Božović, A. M., Mandušić, V.,& Krajnović, M. M.. (2014). Methylation-specific PCR: four steps in primer design. in Central European Journal of Biology, 9(12), 1127-1139.
https://doi.org/10.2478/s11535-014-0324-z

Davidović RS, Božović AM, Mandušić V, Krajnović MM. Methylation-specific PCR: four steps in primer design. in Central European Journal of Biology. 2014;9(12):1127-1139.
doi:10.2478/s11535-014-0324-z .

Davidović, Radoslav S., Božović, Ana M., Mandušić, Vesna, Krajnović, Milena M., "Methylation-specific PCR: four steps in primer design" in Central European Journal of Biology, 9, no. 12 (2014):1127-1139,
https://doi.org/10.2478/s11535-014-0324-z . .

TY  - JOUR
AU  - Božović, Ana M.
AU  - Markićević, Milan
AU  - Dimitrijević, Bogomir B.
AU  - Jovanović-Ćupić, Snežana P.
AU  - Krajnović, Milena M.
AU  - Lukić, Silvana
AU  - Mandušić, Vesna
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5647
AB  - The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ER beta) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ER beta gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ER beta 1 isoform, while ER beta 1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ER beta gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ER alpha) protein levels (q = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ER beta 1 protein levels were negatively correlated with ER alpha protein (q = -0.27, P LT 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ER beta 1-mRNA and/or protein levels.
T2  - Medical Oncology
T1  - Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer
VL  - 30
IS  - 3
DO  - 10.1007/s12032-013-0642-4
ER  - 

@article{
author = "Božović, Ana M. and Markićević, Milan and Dimitrijević, Bogomir B. and Jovanović-Ćupić, Snežana P. and Krajnović, Milena M. and Lukić, Silvana and Mandušić, Vesna",
year = "2013",
abstract = "The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ER beta) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ER beta gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ER beta 1 isoform, while ER beta 1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ER beta gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ER alpha) protein levels (q = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ER beta 1 protein levels were negatively correlated with ER alpha protein (q = -0.27, P LT 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ER beta 1-mRNA and/or protein levels.",
journal = "Medical Oncology",
title = "Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer",
volume = "30",
number = "3",
doi = "10.1007/s12032-013-0642-4"
}

Božović, A. M., Markićević, M., Dimitrijević, B. B., Jovanović-Ćupić, S. P., Krajnović, M. M., Lukić, S.,& Mandušić, V.. (2013). Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer. in Medical Oncology, 30(3).
https://doi.org/10.1007/s12032-013-0642-4

Božović AM, Markićević M, Dimitrijević BB, Jovanović-Ćupić SP, Krajnović MM, Lukić S, Mandušić V. Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer. in Medical Oncology. 2013;30(3).
doi:10.1007/s12032-013-0642-4 .

Božović, Ana M., Markićević, Milan, Dimitrijević, Bogomir B., Jovanović-Ćupić, Snežana P., Krajnović, Milena M., Lukić, Silvana, Mandušić, Vesna, "Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer" in Medical Oncology, 30, no. 3 (2013),
https://doi.org/10.1007/s12032-013-0642-4 . .

TY  - JOUR
AU  - Mandušić, Vesna
AU  - Popov-Celeketic, Dusan
AU  - Nešković-Konstantinović, Zora
AU  - Kanjer, Ksenija
AU  - Božović, Ana M.
AU  - Nikolić-Vukosavljević, Dragica
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4046
AB  - It is well known that breast tumors which are estrogen positive ER(+) are more likely to respond to hormone therapy. However, a certain percentage of ER(+)/PR(+) tumors do not respond to this therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ER), as well as the existence of numerous isoforms/splice variants of both ER alpha and ER beta, suggests that a complex regulation of estrogen action exists. In this study, we analyzed the expression ratio of ER beta 1 isoform and ER beta Delta 5 splice variant mRNAs, and its correlation with ER/PR status by quantitative RT-PCR and clinical and histopathological parameters. We found that the relative proportion of ER beta Delta 5 in the total ER beta 1 transcript pool inversely correlates with the PR level (rho = -0,359, p LT 0,003, Spearman). It may be that the ER beta Delta 5 variant modulates the ERa activity of downstream targets. In addition, we suggest that the determination of the expression profiles of ER alpha and ER beta isoforms and splice variants in the defined groups of patients are necessary for elucidating their involvement in endocrine resistance.
T2  - Archives of Biological Sciences
T1  - Levels of Estrogen Receptor B Splice Variant (Erb Delta 5) Mrna Correlates with Progesterone Receptor in Breast Carcinomas
VL  - 62
IS  - 2
SP  - 257
EP  - 262
DO  - 10.2298/ABS1002257M
ER  - 

@article{
author = "Mandušić, Vesna and Popov-Celeketic, Dusan and Nešković-Konstantinović, Zora and Kanjer, Ksenija and Božović, Ana M. and Nikolić-Vukosavljević, Dragica",
year = "2010",
abstract = "It is well known that breast tumors which are estrogen positive ER(+) are more likely to respond to hormone therapy. However, a certain percentage of ER(+)/PR(+) tumors do not respond to this therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ER), as well as the existence of numerous isoforms/splice variants of both ER alpha and ER beta, suggests that a complex regulation of estrogen action exists. In this study, we analyzed the expression ratio of ER beta 1 isoform and ER beta Delta 5 splice variant mRNAs, and its correlation with ER/PR status by quantitative RT-PCR and clinical and histopathological parameters. We found that the relative proportion of ER beta Delta 5 in the total ER beta 1 transcript pool inversely correlates with the PR level (rho = -0,359, p LT 0,003, Spearman). It may be that the ER beta Delta 5 variant modulates the ERa activity of downstream targets. In addition, we suggest that the determination of the expression profiles of ER alpha and ER beta isoforms and splice variants in the defined groups of patients are necessary for elucidating their involvement in endocrine resistance.",
journal = "Archives of Biological Sciences",
title = "Levels of Estrogen Receptor B Splice Variant (Erb Delta 5) Mrna Correlates with Progesterone Receptor in Breast Carcinomas",
volume = "62",
number = "2",
pages = "257-262",
doi = "10.2298/ABS1002257M"
}

Mandušić, V., Popov-Celeketic, D., Nešković-Konstantinović, Z., Kanjer, K., Božović, A. M.,& Nikolić-Vukosavljević, D.. (2010). Levels of Estrogen Receptor B Splice Variant (Erb Delta 5) Mrna Correlates with Progesterone Receptor in Breast Carcinomas. in Archives of Biological Sciences, 62(2), 257-262.
https://doi.org/10.2298/ABS1002257M

Mandušić V, Popov-Celeketic D, Nešković-Konstantinović Z, Kanjer K, Božović AM, Nikolić-Vukosavljević D. Levels of Estrogen Receptor B Splice Variant (Erb Delta 5) Mrna Correlates with Progesterone Receptor in Breast Carcinomas. in Archives of Biological Sciences. 2010;62(2):257-262.
doi:10.2298/ABS1002257M .

Mandušić, Vesna, Popov-Celeketic, Dusan, Nešković-Konstantinović, Zora, Kanjer, Ksenija, Božović, Ana M., Nikolić-Vukosavljević, Dragica, "Levels of Estrogen Receptor B Splice Variant (Erb Delta 5) Mrna Correlates with Progesterone Receptor in Breast Carcinomas" in Archives of Biological Sciences, 62, no. 2 (2010):257-262,
https://doi.org/10.2298/ABS1002257M . .