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

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

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

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

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

TY  - CONF
AU  - 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 .