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  - JOUR
AU  - Radić, Jelena
AU  - Kožik, Bojana
AU  - Nikolić, Ivan
AU  - Kolarov-Bjelobrk, Ivana
AU  - Vasiljević, Tijana
AU  - Vranjković, Bojana
AU  - Despotović, Sanja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11377
AB  - LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic
target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked
with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the
mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development.
We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of
the HCC tumor microenvironment, formation of premetastatic niches, and epithelial–mesenchymal
transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis,
and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2
inhibitors and discuss their potential in HCC precision treatment.
T2  - International Journal of Molecular Sciences
T1  - Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting
VL  - 24
IS  - 14
SP  - 11745
DO  - 10.3390/ijms241411745
ER  - 

@article{
author = "Radić, Jelena and Kožik, Bojana and Nikolić, Ivan and Kolarov-Bjelobrk, Ivana and Vasiljević, Tijana and Vranjković, Bojana and Despotović, Sanja",
year = "2023",
abstract = "LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic
target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked
with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the
mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development.
We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of
the HCC tumor microenvironment, formation of premetastatic niches, and epithelial–mesenchymal
transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis,
and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2
inhibitors and discuss their potential in HCC precision treatment.",
journal = "International Journal of Molecular Sciences",
title = "Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting",
volume = "24",
number = "14",
pages = "11745",
doi = "10.3390/ijms241411745"
}

Radić, J., Kožik, B., Nikolić, I., Kolarov-Bjelobrk, I., Vasiljević, T., Vranjković, B.,& Despotović, S.. (2023). Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting. in International Journal of Molecular Sciences, 24(14), 11745.
https://doi.org/10.3390/ijms241411745

Radić J, Kožik B, Nikolić I, Kolarov-Bjelobrk I, Vasiljević T, Vranjković B, Despotović S. Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting. in International Journal of Molecular Sciences. 2023;24(14):11745.
doi:10.3390/ijms241411745 .

Radić, Jelena, Kožik, Bojana, Nikolić, Ivan, Kolarov-Bjelobrk, Ivana, Vasiljević, Tijana, Vranjković, Bojana, Despotović, Sanja, "Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting" in International Journal of Molecular Sciences, 24, no. 14 (2023):11745,
https://doi.org/10.3390/ijms241411745 . .

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  - CONF
AU  - Radić, Jelena
AU  - Kolarov Bjelobrk, Ivana
AU  - Nikolić, Ivan
AU  - Vasiljević, Tijana
AU  - Đurić, Aleksandar
AU  - Vidović, Vladimir
AU  - Kožik, Bojana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12636
AB  - Background: Treatment of metastaƟ c colorectal cancer (mCRC) remains a clinical challenge since a certain percentage of paƟ ents with RAS/RAF wild type (wt) tumor do not respond to anƟ -EGFR therapy. The reasons may be a consequence of primary or secondary resistance or the excessive expression of HER2 receptors in paƟ ents with mCRC. The localizaƟ on of the primary tumor (LPT) can also contribute to variable treatment response and disease outcomes since segments of the large bowl represent disƟ ncƟ ve molecular enƟƟ es. The aim of this study was to examine the prognosƟ c value of LPT, as well as to invesƟ gate the role of HER2-receptor expression in paƟ ents with mCRC. PaƟ ents and Methods: This study included 181 paƟ ents (101 leŌ LPT and 80 right LPT) with KRASwt mCRC, who received anƟ -EGFR therapy at the Oncology InsƟ tute of Vojvodina. KRAS mutaƟ on status was determined using Real-Time PCR methodology, while HER2-receptor expression was detected immunohistochemically. The eff ect of anƟ -EGFR anƟ body therapy was analyzed using progression-free survival (PFS) and overall survival (OS) in relaƟ on to the LPT and the HER2-receptor expression. Results: The median OS in paƟ ents with leŌ -side tumors was signifi cantly beƩ er than in paƟ ents with rightside localized tumors (43 vs. 33 months, Mantel-Cox p=0.005; Breslow p=0.001), as well as median PFS (6 vs. 3 months, Mantel-Cox p <0.001; Breslow p<0.001). According to the mulƟ variate Cox regression analysis of OS and PFS, right tumor localizaƟ on also represents an independent prognosƟ c factor (p=0.022; HR 1.46; 95% CI 1.06-2.01; p=0.004; HR 1.60; 95% CI 1.16-2.21, respecƟ vely). The OS of HER2 posiƟ ve paƟ ents is worse than in HER2 negaƟ ve paƟ ents (p = 0.339), while the PFS of HER2 posiƟ ve paƟ ents was signifi cantly worse (p<0.001) compared to HER2 negaƟ ve paƟ ents (despite a relaƟ vely small number of HER2 posiƟ ve paƟ ents). Conclusion: LocalizaƟ on of the primary tumor is an important prognosƟ c marker in the KRASwt mCRC paƟ ents since results demonstrated that paƟ ents with right-sided primary tumors have a staƟ sƟ cally signifi cantly shorter PSF and OS. The role of HER2 receptor expression requires further examinaƟ on, although we noted a low expression level of HER2 receptor in KRASwt mCRC; these paƟ ents also had a shorter PFS and OS.
PB  - Belgrade : Serbian Association for Cancer Research
C3  - Oncology Insights
T1  - Prognostic significance of the localization of the primary tumor and HER2-receptor expression in KRAS wild-type metastatic colorectal cancer treated with anti-EGFR therapy
IS  - 1
SP  - 88
EP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12636
ER  - 

@conference{
author = "Radić, Jelena and Kolarov Bjelobrk, Ivana and Nikolić, Ivan and Vasiljević, Tijana and Đurić, Aleksandar and Vidović, Vladimir and Kožik, Bojana",
year = "2023",
abstract = "Background: Treatment of metastaƟ c colorectal cancer (mCRC) remains a clinical challenge since a certain percentage of paƟ ents with RAS/RAF wild type (wt) tumor do not respond to anƟ -EGFR therapy. The reasons may be a consequence of primary or secondary resistance or the excessive expression of HER2 receptors in paƟ ents with mCRC. The localizaƟ on of the primary tumor (LPT) can also contribute to variable treatment response and disease outcomes since segments of the large bowl represent disƟ ncƟ ve molecular enƟƟ es. The aim of this study was to examine the prognosƟ c value of LPT, as well as to invesƟ gate the role of HER2-receptor expression in paƟ ents with mCRC. PaƟ ents and Methods: This study included 181 paƟ ents (101 leŌ LPT and 80 right LPT) with KRASwt mCRC, who received anƟ -EGFR therapy at the Oncology InsƟ tute of Vojvodina. KRAS mutaƟ on status was determined using Real-Time PCR methodology, while HER2-receptor expression was detected immunohistochemically. The eff ect of anƟ -EGFR anƟ body therapy was analyzed using progression-free survival (PFS) and overall survival (OS) in relaƟ on to the LPT and the HER2-receptor expression. Results: The median OS in paƟ ents with leŌ -side tumors was signifi cantly beƩ er than in paƟ ents with rightside localized tumors (43 vs. 33 months, Mantel-Cox p=0.005; Breslow p=0.001), as well as median PFS (6 vs. 3 months, Mantel-Cox p <0.001; Breslow p<0.001). According to the mulƟ variate Cox regression analysis of OS and PFS, right tumor localizaƟ on also represents an independent prognosƟ c factor (p=0.022; HR 1.46; 95% CI 1.06-2.01; p=0.004; HR 1.60; 95% CI 1.16-2.21, respecƟ vely). The OS of HER2 posiƟ ve paƟ ents is worse than in HER2 negaƟ ve paƟ ents (p = 0.339), while the PFS of HER2 posiƟ ve paƟ ents was signifi cantly worse (p<0.001) compared to HER2 negaƟ ve paƟ ents (despite a relaƟ vely small number of HER2 posiƟ ve paƟ ents). Conclusion: LocalizaƟ on of the primary tumor is an important prognosƟ c marker in the KRASwt mCRC paƟ ents since results demonstrated that paƟ ents with right-sided primary tumors have a staƟ sƟ cally signifi cantly shorter PSF and OS. The role of HER2 receptor expression requires further examinaƟ on, although we noted a low expression level of HER2 receptor in KRASwt mCRC; these paƟ ents also had a shorter PFS and OS.",
publisher = "Belgrade : Serbian Association for Cancer Research",
journal = "Oncology Insights",
title = "Prognostic significance of the localization of the primary tumor and HER2-receptor expression in KRAS wild-type metastatic colorectal cancer treated with anti-EGFR therapy",
number = "1",
pages = "88-88",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12636"
}

Radić, J., Kolarov Bjelobrk, I., Nikolić, I., Vasiljević, T., Đurić, A., Vidović, V.,& Kožik, B.. (2023). Prognostic significance of the localization of the primary tumor and HER2-receptor expression in KRAS wild-type metastatic colorectal cancer treated with anti-EGFR therapy. in Oncology Insights
Belgrade : Serbian Association for Cancer Research.(1), 88-88.
https://hdl.handle.net/21.15107/rcub_vinar_12636

Radić J, Kolarov Bjelobrk I, Nikolić I, Vasiljević T, Đurić A, Vidović V, Kožik B. Prognostic significance of the localization of the primary tumor and HER2-receptor expression in KRAS wild-type metastatic colorectal cancer treated with anti-EGFR therapy. in Oncology Insights. 2023;(1):88-88.
https://hdl.handle.net/21.15107/rcub_vinar_12636 .

Radić, Jelena, Kolarov Bjelobrk, Ivana, Nikolić, Ivan, Vasiljević, Tijana, Đurić, Aleksandar, Vidović, Vladimir, Kožik, Bojana, "Prognostic significance of the localization of the primary tumor and HER2-receptor expression in KRAS wild-type metastatic colorectal cancer treated with anti-EGFR therapy" in Oncology Insights, no. 1 (2023):88-88,
https://hdl.handle.net/21.15107/rcub_vinar_12636 .

TY  - CONF
AU  - Đurić, Mladen
AU  - Kožik, Bojana
AU  - Vasiljević, Tijana
AU  - Đermanović, Aleksandar
AU  - Stanulović, Nevena
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12637
AB  - Background: Rectal carcinoma (RC), a common malignancy of the gastrointesƟ nal tract, remains a great clinical challenge due to the increased risk of local and/or systemic recurrence. The mechanism of primary tumor progression and disseminaƟ on may be the crucial prognosƟ c factor. Direct vascular spread, especially venous invasion, has been previously recognized and validated as an important predictor of adverse prognosis. 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, increased risk of local recurrence, systemic recurrence, and death. The aim of this study is to examine the prognosƟ c value of pathologically detected EMVI and its relaƟ onship with other available clinicopathological parameters of paƟ ents with RC. PaƟ ents and Methods: This retrospecƟ ve study included 100 untreated and non-metastaƟ c RC paƟ ents (50 EMVI+ and 50 EMVI-) who underwent curaƟ ve resecƟ on between January 2016 and June 2018 and were followed for the next fi ve years (median follow-up of 71.1 months). The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological secƟ ons of postoperaƟ ve tumor specimens samples, confi rmed by a consultant pathologist in arbitrary cases, and in accordance with validated College of American Pathologist (CAP) guidelines. Results: The presence of EMVI within a selected cohort of RC paƟ ents signifi cantly associated with female gender (p=0.039), T4 stage (p=<0.001), N2 stage (p=<0.001), less number (n≤3) of involved lymph nodes (p=<0.001), excessive lymphaƟ c infi ltraƟ on (p=0.044), presence of perineural invasion (p=0.002), posiƟ ve circumferenƟ al margin (CRM) (p=0.003), and TNMIII stage (p=<0.001). In addiƟ on, within EMVI+ paƟ ents, metastases, dominantly in the liver (13/19, 68%), and death outcomes were more frequent events (p=0.013 and p=0.032, respecƟ vely), while survival analyses revealed that EMVI+ paƟ ents had signifi cantly shorter overall survival (OS, p=0.035) and disease-free survival (DFS, p=0.030). Conclusion: Obtained results strongly suggest that the EMVI type of vascular invasion, considered independently of classical stage parameters and separately from lymphaƟ c invasion, has the potenƟ al to be a reliable predictor of the course and outcome of the disease, which should be confi rmed on a larger cohort of paƟ ents with RC.
PB  - Belgrade : Serbian Association for Cancer Research
C3  - Oncology Insights
T1  - Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma
IS  - 1
SP  - 90
EP  - 90
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12637
ER  - 

@conference{
author = "Đurić, Mladen and Kožik, Bojana and Vasiljević, Tijana and Đermanović, Aleksandar and Stanulović, Nevena",
year = "2023",
abstract = "Background: Rectal carcinoma (RC), a common malignancy of the gastrointesƟ nal tract, remains a great clinical challenge due to the increased risk of local and/or systemic recurrence. The mechanism of primary tumor progression and disseminaƟ on may be the crucial prognosƟ c factor. Direct vascular spread, especially venous invasion, has been previously recognized and validated as an important predictor of adverse prognosis. 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, increased risk of local recurrence, systemic recurrence, and death. The aim of this study is to examine the prognosƟ c value of pathologically detected EMVI and its relaƟ onship with other available clinicopathological parameters of paƟ ents with RC. PaƟ ents and Methods: This retrospecƟ ve study included 100 untreated and non-metastaƟ c RC paƟ ents (50 EMVI+ and 50 EMVI-) who underwent curaƟ ve resecƟ on between January 2016 and June 2018 and were followed for the next fi ve years (median follow-up of 71.1 months). The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological secƟ ons of postoperaƟ ve tumor specimens samples, confi rmed by a consultant pathologist in arbitrary cases, and in accordance with validated College of American Pathologist (CAP) guidelines. Results: The presence of EMVI within a selected cohort of RC paƟ ents signifi cantly associated with female gender (p=0.039), T4 stage (p=<0.001), N2 stage (p=<0.001), less number (n≤3) of involved lymph nodes (p=<0.001), excessive lymphaƟ c infi ltraƟ on (p=0.044), presence of perineural invasion (p=0.002), posiƟ ve circumferenƟ al margin (CRM) (p=0.003), and TNMIII stage (p=<0.001). In addiƟ on, within EMVI+ paƟ ents, metastases, dominantly in the liver (13/19, 68%), and death outcomes were more frequent events (p=0.013 and p=0.032, respecƟ vely), while survival analyses revealed that EMVI+ paƟ ents had signifi cantly shorter overall survival (OS, p=0.035) and disease-free survival (DFS, p=0.030). Conclusion: Obtained results strongly suggest that the EMVI type of vascular invasion, considered independently of classical stage parameters and separately from lymphaƟ c invasion, has the potenƟ al to be a reliable predictor of the course and outcome of the disease, which should be confi rmed on a larger cohort of paƟ ents with RC.",
publisher = "Belgrade : Serbian Association for Cancer Research",
journal = "Oncology Insights",
title = "Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma",
number = "1",
pages = "90-90",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12637"
}

Đurić, M., Kožik, B., Vasiljević, T., Đermanović, A.,& Stanulović, N.. (2023). Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma. in Oncology Insights
Belgrade : Serbian Association for Cancer Research.(1), 90-90.
https://hdl.handle.net/21.15107/rcub_vinar_12637

Đurić M, Kožik B, Vasiljević T, Đermanović A, Stanulović N. Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma. in Oncology Insights. 2023;(1):90-90.
https://hdl.handle.net/21.15107/rcub_vinar_12637 .

Đurić, Mladen, Kožik, Bojana, Vasiljević, Tijana, Đermanović, Aleksandar, Stanulović, Nevena, "Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma" in Oncology Insights, no. 1 (2023):90-90,
https://hdl.handle.net/21.15107/rcub_vinar_12637 .

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  - Jovanović-Ćupić, Snežana
AU  - Šiljić, Marina
AU  - Ćirković, Valentina
AU  - Petrović, Nina
AU  - Kožik, Bojana
AU  - Krajnović, Milena
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12051
AB  - Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients.
T2  - Archives of Biological Sciences
T1  - Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia
VL  - 75
IS  - 3
SP  - 251
EP  - 262
DO  - 10.2298/ABS230316020K
ER  - 

@article{
author = "Kokanov, Nikola and Jovanović-Ćupić, Snežana and Šiljić, Marina and Ćirković, Valentina and Petrović, Nina and Kožik, Bojana and Krajnović, Milena",
year = "2023",
abstract = "Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients.",
journal = "Archives of Biological Sciences",
title = "Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia",
volume = "75",
number = "3",
pages = "251-262",
doi = "10.2298/ABS230316020K"
}

Kokanov, N., Jovanović-Ćupić, S., Šiljić, M., Ćirković, V., Petrović, N., Kožik, B.,& Krajnović, M.. (2023). Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia. in Archives of Biological Sciences, 75(3), 251-262.
https://doi.org/10.2298/ABS230316020K

Kokanov N, Jovanović-Ćupić S, Šiljić M, Ćirković V, Petrović N, Kožik B, Krajnović M. Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia. in Archives of Biological Sciences. 2023;75(3):251-262.
doi:10.2298/ABS230316020K .

Kokanov, Nikola, Jovanović-Ćupić, Snežana, Šiljić, Marina, Ćirković, Valentina, Petrović, Nina, Kožik, Bojana, Krajnović, Milena, "Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia" in Archives of Biological Sciences, 75, no. 3 (2023):251-262,
https://doi.org/10.2298/ABS230316020K . .

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  - Kožik, Bojana
AU  - Kokanov, Nikola
AU  - Knežević-Ušaj, Slavica
AU  - Nikolić, Ivan
AU  - Davidović, Radoslav S.
AU  - Jovanović-Ćupić, Snežana P.
AU  - Krajnović, Milena M.
PY  - 2018
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641800030K
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8002
AB  - Methylation of p16 and p14 genes is a common event in colorectal cancers; however, their exact role in the prediction of patients' outcome is unclear. We conducted this retrospective study to evaluate their potential predictive and/or prognostic roles. Methylation-specific PCR was used to examine the methylation status of p16 and p14 in pretherapeutic and preoperative biopsy specimens of 60 patients with locally advanced rectal cancer. The methylation status of the examined genes did not affect the response to preoperative chemoradiotherapy (CRT), recurrence rate and overall survival. However, patients with a simultaneous presence of either p16 or p14 methylation and high vascular endothelial growth factor (VEGF) expression showed a significantly worse response to CRT (p=0.005 and p=0.038, respectively). Moreover, patients with both p16 methylation and high VEGF expression had significantly shorter overall survival (p=0.010), while no such association was found in patients with p14 methylation and high VEGF expression. On the other hand, a subgroup of patients with p16 methylation and low VEGF and high epidermal growth factor receptor (EGFR) expression showed a significantly better response to CRT (p=0.024). The obtained results point to the importance of p16 and p14 methylation analyses in combination with VEGF and EGFR expression, aimed at better predicting treatment response and patient outcome. © 2018 by the Serbian Biological Society.
T2  - Archives of Biological Sciences
T1  - Methylation status of p16 and p14 genes in locally advanced rectal cancer: Potential clinical implication
VL  - 70
IS  - 4
SP  - 681
EP  - 690
DO  - 10.2298/ABS180316030K
ER  - 

@article{
author = "Kožik, Bojana and Kokanov, Nikola and Knežević-Ušaj, Slavica and Nikolić, Ivan and Davidović, Radoslav S. and Jovanović-Ćupić, Snežana P. and Krajnović, Milena M.",
year = "2018",
abstract = "Methylation of p16 and p14 genes is a common event in colorectal cancers; however, their exact role in the prediction of patients' outcome is unclear. We conducted this retrospective study to evaluate their potential predictive and/or prognostic roles. Methylation-specific PCR was used to examine the methylation status of p16 and p14 in pretherapeutic and preoperative biopsy specimens of 60 patients with locally advanced rectal cancer. The methylation status of the examined genes did not affect the response to preoperative chemoradiotherapy (CRT), recurrence rate and overall survival. However, patients with a simultaneous presence of either p16 or p14 methylation and high vascular endothelial growth factor (VEGF) expression showed a significantly worse response to CRT (p=0.005 and p=0.038, respectively). Moreover, patients with both p16 methylation and high VEGF expression had significantly shorter overall survival (p=0.010), while no such association was found in patients with p14 methylation and high VEGF expression. On the other hand, a subgroup of patients with p16 methylation and low VEGF and high epidermal growth factor receptor (EGFR) expression showed a significantly better response to CRT (p=0.024). The obtained results point to the importance of p16 and p14 methylation analyses in combination with VEGF and EGFR expression, aimed at better predicting treatment response and patient outcome. © 2018 by the Serbian Biological Society.",
journal = "Archives of Biological Sciences",
title = "Methylation status of p16 and p14 genes in locally advanced rectal cancer: Potential clinical implication",
volume = "70",
number = "4",
pages = "681-690",
doi = "10.2298/ABS180316030K"
}

Kožik, B., Kokanov, N., Knežević-Ušaj, S., Nikolić, I., Davidović, R. S., Jovanović-Ćupić, S. P.,& Krajnović, M. M.. (2018). Methylation status of p16 and p14 genes in locally advanced rectal cancer: Potential clinical implication. in Archives of Biological Sciences, 70(4), 681-690.
https://doi.org/10.2298/ABS180316030K

Kožik B, Kokanov N, Knežević-Ušaj S, Nikolić I, Davidović RS, Jovanović-Ćupić SP, Krajnović MM. Methylation status of p16 and p14 genes in locally advanced rectal cancer: Potential clinical implication. in Archives of Biological Sciences. 2018;70(4):681-690.
doi:10.2298/ABS180316030K .

Kožik, Bojana, Kokanov, Nikola, Knežević-Ušaj, Slavica, Nikolić, Ivan, Davidović, Radoslav S., Jovanović-Ćupić, Snežana P., Krajnović, Milena M., "Methylation status of p16 and p14 genes in locally advanced rectal cancer: Potential clinical implication" in Archives of Biological Sciences, 70, no. 4 (2018):681-690,
https://doi.org/10.2298/ABS180316030K . .

TY  - CONF
AU  - Kožik, Bojana
AU  - Kokanov, Nikola
AU  - Knežević-Ušaj, Slavica
AU  - Nikolić, Ivan
AU  - Davidović, Radoslav
AU  - Jovanović Ćupić, Snežana
AU  - Krajnović, Milena
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12805
AB  - Background: Preoperative chemoradiotherapy (CRT) represents the standard treatment for patients with locally advanced rectal cancer. Since only subset of patients has benefit from this preoperative treatment, development of reliable molecular biomarkers is required. In this retrospective study, we investigated methylation status of p16 and p14 tumor suppressor genes in locally advanced rectal cancer, in order to evaluate their potential predictive and prognostic role. Methods: Methylation-specific PCR was used to examine methylation status of p16 and p14 genes in pretherapeutic and preoperative biopsy specimens of 60 patients with locally advanced rectal cancer. Results: Aberrant methylation of p16 and p14 genes was detected in 43.3% (26/60) and 39.6% (23/58) of cases, respectively. In general, p16 and p14 methylation status did not affect the response to CRT, recurrences rate and overall survival. However, patients with simultaneous presence of either p16 or p14 methylation and high vascular endothelial growth factor (VEGF) expression showed significantly worse response to CRT (p = 0.005 and p = 0.038, respectively). In addition, tendency toward more frequent local recurrences and metastasis was observed in cases with concurrent presence of methylation of either p16 or p14 gene and high VEGF expression (p = 0.075 and p = 0.072, respectively), while patients with both of p16 methylation and high VEGF expression had significantly shorter overall survival (p = 0.010). Conclusion: Obtained results strongly suggest the importance of p16 and p14 methylation analyses in combination with other parameters, particularly VEGF expression, in order to better predict treatment response and patient outcome.
PB  - Belgrade : University of Belgrade, Faculty of Biology
C3  - CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts
T1  - Combined analysis of p16 and p14 methylation and VEGF expression status could predict more aggressive phenotype of locally advanced rectal cancers
SP  - 100
EP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12805
ER  - 

@conference{
author = "Kožik, Bojana and Kokanov, Nikola and Knežević-Ušaj, Slavica and Nikolić, Ivan and Davidović, Radoslav and Jovanović Ćupić, Snežana and Krajnović, Milena",
year = "2017",
abstract = "Background: Preoperative chemoradiotherapy (CRT) represents the standard treatment for patients with locally advanced rectal cancer. Since only subset of patients has benefit from this preoperative treatment, development of reliable molecular biomarkers is required. In this retrospective study, we investigated methylation status of p16 and p14 tumor suppressor genes in locally advanced rectal cancer, in order to evaluate their potential predictive and prognostic role. Methods: Methylation-specific PCR was used to examine methylation status of p16 and p14 genes in pretherapeutic and preoperative biopsy specimens of 60 patients with locally advanced rectal cancer. Results: Aberrant methylation of p16 and p14 genes was detected in 43.3% (26/60) and 39.6% (23/58) of cases, respectively. In general, p16 and p14 methylation status did not affect the response to CRT, recurrences rate and overall survival. However, patients with simultaneous presence of either p16 or p14 methylation and high vascular endothelial growth factor (VEGF) expression showed significantly worse response to CRT (p = 0.005 and p = 0.038, respectively). In addition, tendency toward more frequent local recurrences and metastasis was observed in cases with concurrent presence of methylation of either p16 or p14 gene and high VEGF expression (p = 0.075 and p = 0.072, respectively), while patients with both of p16 methylation and high VEGF expression had significantly shorter overall survival (p = 0.010). Conclusion: Obtained results strongly suggest the importance of p16 and p14 methylation analyses in combination with other parameters, particularly VEGF expression, in order to better predict treatment response and patient outcome.",
publisher = "Belgrade : University of Belgrade, Faculty of Biology",
journal = "CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts",
title = "Combined analysis of p16 and p14 methylation and VEGF expression status could predict more aggressive phenotype of locally advanced rectal cancers",
pages = "100-100",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12805"
}

Kožik, B., Kokanov, N., Knežević-Ušaj, S., Nikolić, I., Davidović, R., Jovanović Ćupić, S.,& Krajnović, M.. (2017). Combined analysis of p16 and p14 methylation and VEGF expression status could predict more aggressive phenotype of locally advanced rectal cancers. in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts
Belgrade : University of Belgrade, Faculty of Biology., 100-100.
https://hdl.handle.net/21.15107/rcub_vinar_12805

Kožik B, Kokanov N, Knežević-Ušaj S, Nikolić I, Davidović R, Jovanović Ćupić S, Krajnović M. Combined analysis of p16 and p14 methylation and VEGF expression status could predict more aggressive phenotype of locally advanced rectal cancers. in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts. 2017;:100-100.
https://hdl.handle.net/21.15107/rcub_vinar_12805 .

Kožik, Bojana, Kokanov, Nikola, Knežević-Ušaj, Slavica, Nikolić, Ivan, Davidović, Radoslav, Jovanović Ćupić, Snežana, Krajnović, Milena, "Combined analysis of p16 and p14 methylation and VEGF expression status could predict more aggressive phenotype of locally advanced rectal cancers" in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts (2017):100-100,
https://hdl.handle.net/21.15107/rcub_vinar_12805 .

TY  - JOUR
AU  - Krajnović, Milena M.
AU  - Marković, Bojana
AU  - Knežević-Ušaj, Slavica
AU  - Nikolic, Ivan
AU  - Stanojevic, Maja
AU  - Nikolić, Valentina
AU  - Siljic, Marina
AU  - Jovanović-Ćupić, Snežana P.
AU  - Dimitrijević, Bogomir B.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1164
AB  - In this study, we investigated the mutation status of KRAS gene in pretherapeutic and preoperative biopsies in 63 specimens of locally advanced rectal cancers in order to evaluate its potential predictive and/or prognostic role. Regions of interest of KRAS exon 2 were amplified and visualized on 2% agarose gel. Obtained PCR products were subjected to direct sequencing. KRAS mutations were detected in 35% of patients, 91% of which were located in codon 12 and 9% in codon 13. In general, KRAS mutation status did not affect the response to neoadjuvant chemoradiotherapy (CRT). However, patients harboring mutated KRAS gene, simultaneously with high vascular endothelial growth factor (VEGF) expression, exhibited a worse response to CRT (p = 0.030), a more frequent appearance of local recurrences and distant metastasis (p = 0.003), and shorter overall survival (p = 0.001) compared to all others. On the contrary, patients with GGT GT GCT KRAS mutation exhibited a significantly better response to CRT than those with any other type of KRAS mutation (p = 0.017). Moreover, the presence of GGT GT GCT mutation was associated with low VEGF and Ki67 expression (p = 0.012 in both cases), parameters related to less aggressiveness of the disease. Our results suggest that KRAS mutation status could have some predictive and prognostic importance in rectal cancer when analyzed together with other parameters, such as VEGF and Ki67 expression. In addition, it seems that not only the presence but the type of KRAS mutation is important for examining its impact on CRT response. (C) 2016 Elsevier GmbH. All rights reserved.
T2  - Pathology Research and Practice
T1  - Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics
VL  - 212
IS  - 7
SP  - 598
EP  - 603
DO  - 10.1016/j.prp.2016.02.018
ER  - 

@article{
author = "Krajnović, Milena M. and Marković, Bojana and Knežević-Ušaj, Slavica and Nikolic, Ivan and Stanojevic, Maja and Nikolić, Valentina and Siljic, Marina and Jovanović-Ćupić, Snežana P. and Dimitrijević, Bogomir B.",
year = "2016",
abstract = "In this study, we investigated the mutation status of KRAS gene in pretherapeutic and preoperative biopsies in 63 specimens of locally advanced rectal cancers in order to evaluate its potential predictive and/or prognostic role. Regions of interest of KRAS exon 2 were amplified and visualized on 2% agarose gel. Obtained PCR products were subjected to direct sequencing. KRAS mutations were detected in 35% of patients, 91% of which were located in codon 12 and 9% in codon 13. In general, KRAS mutation status did not affect the response to neoadjuvant chemoradiotherapy (CRT). However, patients harboring mutated KRAS gene, simultaneously with high vascular endothelial growth factor (VEGF) expression, exhibited a worse response to CRT (p = 0.030), a more frequent appearance of local recurrences and distant metastasis (p = 0.003), and shorter overall survival (p = 0.001) compared to all others. On the contrary, patients with GGT GT GCT KRAS mutation exhibited a significantly better response to CRT than those with any other type of KRAS mutation (p = 0.017). Moreover, the presence of GGT GT GCT mutation was associated with low VEGF and Ki67 expression (p = 0.012 in both cases), parameters related to less aggressiveness of the disease. Our results suggest that KRAS mutation status could have some predictive and prognostic importance in rectal cancer when analyzed together with other parameters, such as VEGF and Ki67 expression. In addition, it seems that not only the presence but the type of KRAS mutation is important for examining its impact on CRT response. (C) 2016 Elsevier GmbH. All rights reserved.",
journal = "Pathology Research and Practice",
title = "Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics",
volume = "212",
number = "7",
pages = "598-603",
doi = "10.1016/j.prp.2016.02.018"
}

Krajnović, M. M., Marković, B., Knežević-Ušaj, S., Nikolic, I., Stanojevic, M., Nikolić, V., Siljic, M., Jovanović-Ćupić, S. P.,& Dimitrijević, B. B.. (2016). Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics. in Pathology Research and Practice, 212(7), 598-603.
https://doi.org/10.1016/j.prp.2016.02.018

Krajnović MM, Marković B, Knežević-Ušaj S, Nikolic I, Stanojevic M, Nikolić V, Siljic M, Jovanović-Ćupić SP, Dimitrijević BB. Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics. in Pathology Research and Practice. 2016;212(7):598-603.
doi:10.1016/j.prp.2016.02.018 .

Krajnović, Milena M., Marković, Bojana, Knežević-Ušaj, Slavica, Nikolic, Ivan, Stanojevic, Maja, Nikolić, Valentina, Siljic, Marina, Jovanović-Ćupić, Snežana P., Dimitrijević, Bogomir B., "Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics" in Pathology Research and Practice, 212, no. 7 (2016):598-603,
https://doi.org/10.1016/j.prp.2016.02.018 . .

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 .