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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - 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  - JOUR
AU  - Jovanović-Ćupić, Snežana P.
AU  - Glišić, Sanja
AU  - Stanojevic, Maja
AU  - Nozic, Darko
AU  - Petrović, Nina
AU  - Mandušić, Vesna
AU  - Krajnović, Milena M.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1032
AB  - The goal of this study was to identify host and viral factors affecting the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment in patients with chronic hepatitis C genotype 1b. Baseline characteristics of the patients and sequences within the p7 region were analyzed in pre-treatment serum samples from 53 individuals with chronic hepatitis C genotype 1b and related to the outcome of therapy. We found a significant correlation between age and response to therapy (p LT 0.001). Furthermore, the pre-treatment viral load was closely associated with the stage of liver fibrosis (p LT 0.001). The presence of fewer than 4 mutations and age above 40 were significantly associated with non-response (NR) (p LT 0.001). Our findings may be useful for estimating the likelihood of achieving a sustained virologic response (SVR) in patients who are chronically infected with hepatitis C virus genotype 1b.
PB  - Springer
T2  - Archives of Virology
T1  - The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia
VL  - 161
IS  - 5
SP  - 1189
EP  - 1198
DO  - 10.1007/s00705-016-2777-z
ER  - 

@article{
author = "Jovanović-Ćupić, Snežana P. and Glišić, Sanja and Stanojevic, Maja and Nozic, Darko and Petrović, Nina and Mandušić, Vesna and Krajnović, Milena M.",
year = "2016",
abstract = "The goal of this study was to identify host and viral factors affecting the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment in patients with chronic hepatitis C genotype 1b. Baseline characteristics of the patients and sequences within the p7 region were analyzed in pre-treatment serum samples from 53 individuals with chronic hepatitis C genotype 1b and related to the outcome of therapy. We found a significant correlation between age and response to therapy (p LT 0.001). Furthermore, the pre-treatment viral load was closely associated with the stage of liver fibrosis (p LT 0.001). The presence of fewer than 4 mutations and age above 40 were significantly associated with non-response (NR) (p LT 0.001). Our findings may be useful for estimating the likelihood of achieving a sustained virologic response (SVR) in patients who are chronically infected with hepatitis C virus genotype 1b.",
publisher = "Springer",
journal = "Archives of Virology",
title = "The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia",
volume = "161",
number = "5",
pages = "1189-1198",
doi = "10.1007/s00705-016-2777-z"
}

Jovanović-Ćupić, S. P., Glišić, S., Stanojevic, M., Nozic, D., Petrović, N., Mandušić, V.,& Krajnović, M. M.. (2016). The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia. in Archives of Virology
Springer., 161(5), 1189-1198.
https://doi.org/10.1007/s00705-016-2777-z

Jovanović-Ćupić SP, Glišić S, Stanojevic M, Nozic D, Petrović N, Mandušić V, Krajnović MM. The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia. in Archives of Virology. 2016;161(5):1189-1198.
doi:10.1007/s00705-016-2777-z .

Jovanović-Ćupić, Snežana P., Glišić, Sanja, Stanojevic, Maja, Nozic, Darko, Petrović, Nina, Mandušić, Vesna, Krajnović, Milena M., "The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia" in Archives of Virology, 161, no. 5 (2016):1189-1198,
https://doi.org/10.1007/s00705-016-2777-z . .

TY  - JOUR
AU  - Petrović, Nina
AU  - Davidović, Radoslav S.
AU  - Jovanović-Ćupić, Snežana P.
AU  - Krajnović, Milena M.
AU  - Lukić, Silvana
AU  - Petrović, Milan
AU  - Roganović, Jelena
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1308
AB  - Breast cancer (BC) is a heterogeneous group of diseases that still represents a major cause of death in the female population. MicroRNAs (miRNAs, miRs), such as miR-221 and miR-222, have been shown to be involved in BC pathology by acting via its target genes such as tissue inhibitor of metalloproteinase 3 (TIMP3). The main goals of this study were to find differences in miR-221/222 levels of expression in BC groups based on invasiveness, and to investigate the association with estrogen receptor (ER), TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of patients and tumors. In this study, we measured levels of miR-221/222 in 63 breast tissue samples by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using TaqMan(A (R)) technology and immunohistochemistry. miR-221/222 levels varied significantly across groups based on invasiveness (P LT 0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER (P = 0.001, r = -0.714, and P = 0.013, r = -0.585, respectively). In invasive breast carcinomas associated with non-invasive tumors, miR-222 was inversely associated with ER (P = 0.039, r = -0.620). Pure invasive BCs showed a positive correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508, and P = 0.010, r = 0.497, respectively). An increase in miR-221/222 might be an important event for in situ carcinoma formation, and miR-221/222 may be important molecules that highlight potential differences between invasive breast carcinomas associated with non-invasive and pure invasive BCs.
T2  - Molecular Diagnosis and Therapy
T1  - Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels
VL  - 20
IS  - 6
SP  - 603
EP  - 615
DO  - 10.1007/s40291-016-0230-3
ER  - 

@article{
author = "Petrović, Nina and Davidović, Radoslav S. and Jovanović-Ćupić, Snežana P. and Krajnović, Milena M. and Lukić, Silvana and Petrović, Milan and Roganović, Jelena",
year = "2016",
abstract = "Breast cancer (BC) is a heterogeneous group of diseases that still represents a major cause of death in the female population. MicroRNAs (miRNAs, miRs), such as miR-221 and miR-222, have been shown to be involved in BC pathology by acting via its target genes such as tissue inhibitor of metalloproteinase 3 (TIMP3). The main goals of this study were to find differences in miR-221/222 levels of expression in BC groups based on invasiveness, and to investigate the association with estrogen receptor (ER), TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of patients and tumors. In this study, we measured levels of miR-221/222 in 63 breast tissue samples by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using TaqMan(A (R)) technology and immunohistochemistry. miR-221/222 levels varied significantly across groups based on invasiveness (P LT 0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER (P = 0.001, r = -0.714, and P = 0.013, r = -0.585, respectively). In invasive breast carcinomas associated with non-invasive tumors, miR-222 was inversely associated with ER (P = 0.039, r = -0.620). Pure invasive BCs showed a positive correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508, and P = 0.010, r = 0.497, respectively). An increase in miR-221/222 might be an important event for in situ carcinoma formation, and miR-221/222 may be important molecules that highlight potential differences between invasive breast carcinomas associated with non-invasive and pure invasive BCs.",
journal = "Molecular Diagnosis and Therapy",
title = "Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels",
volume = "20",
number = "6",
pages = "603-615",
doi = "10.1007/s40291-016-0230-3"
}

Petrović, N., Davidović, R. S., Jovanović-Ćupić, S. P., Krajnović, M. M., Lukić, S., Petrović, M.,& Roganović, J.. (2016). Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels. in Molecular Diagnosis and Therapy, 20(6), 603-615.
https://doi.org/10.1007/s40291-016-0230-3

Petrović N, Davidović RS, Jovanović-Ćupić SP, Krajnović MM, Lukić S, Petrović M, Roganović J. Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels. in Molecular Diagnosis and Therapy. 2016;20(6):603-615.
doi:10.1007/s40291-016-0230-3 .

Petrović, Nina, Davidović, Radoslav S., Jovanović-Ćupić, Snežana P., Krajnović, Milena M., Lukić, Silvana, Petrović, Milan, Roganović, Jelena, "Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels" in Molecular Diagnosis and Therapy, 20, no. 6 (2016):603-615,
https://doi.org/10.1007/s40291-016-0230-3 . .

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

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

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

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

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

TY  - JOUR
AU  - Petrović, Nina
AU  - Jovanović-Ćupić, Snežana P.
AU  - Brajušković, Goran
AU  - Lukić, Silvana
AU  - Roganović, Jelena
AU  - Krajnović, Milena M.
AU  - Mandušić, Vesna
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/862
AB  - Invasive ductal carcinomas with a non-invasive component (IDC-DCIS) are classified as a group of invasive breast carcinomas, together with pure invasive ductal carcinomas of the breast (IDC). MicroRNA-21 (miR-21) has been characterized as a factor of breast cancer invasiveness, however the difference in miR-21 expression levels between IDC-DCIS and pure IDC tumors and the correlations with standard diagnostic and prognostic parameters inside the IDC-DCIS group are unknown. Our aim was to determine if miR-21 had the ability to distinguish these two invasive breast cancer groups. Levels of miR-21 expression were measured by a stem-loop quantitative Real-Time PCR (RT-qPCR) method. Expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and proliferative index Ki-67 were evaluated by immunohistochemistry. IDC-DCIS tumors had significantly lower levels of miR-21 expression in grade 2 (P=0.003, Mann-Whitney U test), ER positive (P=0.025, Mann-Whitney U test) and PR positive tumors (P=0.024, Mann-Whitney U test) than pure IDCs. miR-21 levels showed a different pattern of expression in IDC-DCIS compared to IDC tumors, which is based on the difference in miR-21 expression between Her-2 negative and Her-2 positive IDC-DCIS tumors (P=0.030, Mann-Whitney U test) and high negative correlation of miR-21 levels with PR levels (rho=-0.886, P=0.006, Spearman correlation). According to our results, IDC-DCIS breast carcinomas act in a different manner in pure IDC tumors with regard to the relations between miR-21 expression levels and the standard diagnostic and prognostic parameters, such as Her-2 status, ER and PR status and protein levels.
T2  - Archives of Biological Sciences
T1  - Micro Rna-21 Expression Levels in Invasive Breast Carcinoma with a Non-Invasive Component
VL  - 67
IS  - 4
SP  - 1285
EP  - 1295
DO  - 10.2298/ABS150327105P
ER  - 

@article{
author = "Petrović, Nina and Jovanović-Ćupić, Snežana P. and Brajušković, Goran and Lukić, Silvana and Roganović, Jelena and Krajnović, Milena M. and Mandušić, Vesna",
year = "2015",
abstract = "Invasive ductal carcinomas with a non-invasive component (IDC-DCIS) are classified as a group of invasive breast carcinomas, together with pure invasive ductal carcinomas of the breast (IDC). MicroRNA-21 (miR-21) has been characterized as a factor of breast cancer invasiveness, however the difference in miR-21 expression levels between IDC-DCIS and pure IDC tumors and the correlations with standard diagnostic and prognostic parameters inside the IDC-DCIS group are unknown. Our aim was to determine if miR-21 had the ability to distinguish these two invasive breast cancer groups. Levels of miR-21 expression were measured by a stem-loop quantitative Real-Time PCR (RT-qPCR) method. Expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and proliferative index Ki-67 were evaluated by immunohistochemistry. IDC-DCIS tumors had significantly lower levels of miR-21 expression in grade 2 (P=0.003, Mann-Whitney U test), ER positive (P=0.025, Mann-Whitney U test) and PR positive tumors (P=0.024, Mann-Whitney U test) than pure IDCs. miR-21 levels showed a different pattern of expression in IDC-DCIS compared to IDC tumors, which is based on the difference in miR-21 expression between Her-2 negative and Her-2 positive IDC-DCIS tumors (P=0.030, Mann-Whitney U test) and high negative correlation of miR-21 levels with PR levels (rho=-0.886, P=0.006, Spearman correlation). According to our results, IDC-DCIS breast carcinomas act in a different manner in pure IDC tumors with regard to the relations between miR-21 expression levels and the standard diagnostic and prognostic parameters, such as Her-2 status, ER and PR status and protein levels.",
journal = "Archives of Biological Sciences",
title = "Micro Rna-21 Expression Levels in Invasive Breast Carcinoma with a Non-Invasive Component",
volume = "67",
number = "4",
pages = "1285-1295",
doi = "10.2298/ABS150327105P"
}

Petrović, N., Jovanović-Ćupić, S. P., Brajušković, G., Lukić, S., Roganović, J., Krajnović, M. M.,& Mandušić, V.. (2015). Micro Rna-21 Expression Levels in Invasive Breast Carcinoma with a Non-Invasive Component. in Archives of Biological Sciences, 67(4), 1285-1295.
https://doi.org/10.2298/ABS150327105P

Petrović N, Jovanović-Ćupić SP, Brajušković G, Lukić S, Roganović J, Krajnović MM, Mandušić V. Micro Rna-21 Expression Levels in Invasive Breast Carcinoma with a Non-Invasive Component. in Archives of Biological Sciences. 2015;67(4):1285-1295.
doi:10.2298/ABS150327105P .

Petrović, Nina, Jovanović-Ćupić, Snežana P., Brajušković, Goran, Lukić, Silvana, Roganović, Jelena, Krajnović, Milena M., Mandušić, Vesna, "Micro Rna-21 Expression Levels in Invasive Breast Carcinoma with a Non-Invasive Component" in Archives of Biological Sciences, 67, no. 4 (2015):1285-1295,
https://doi.org/10.2298/ABS150327105P . .

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

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

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

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

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

TY  - JOUR
AU  - Krajnović, Milena M.
AU  - Jovanovic, Maja Perunicic
AU  - Mihaljevic, Biljana
AU  - Andelic, Bosko
AU  - Tarabar, Olivera
AU  - Knežević-Ušaj, Slavica
AU  - Krtolica-Žikić, Koviljka
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/192
AB  - In this study, methylation-specific polymerase chain reaction was used to investigate the potential prognostic significance of the methylation status of p15, p16, MGMT, and DAPK genes in 51 specimens of diffuse large B-cell lymphoma (DLBCL). Hypermethylation of p15 gene was significantly more prevalent in patients without relapse (p = 0.001) and there was a trend toward more frequent presence of p15 methylation in patients without death outcome within 5-year follow-up period (p = 0.086) Also, there was a trend toward accumulation of p15 methylation with favorable clinicopathological parameters including: age 60 years (p = 0.091), normal levels of lactate dehydrogenase (p = 0.090), Eastern Cooperative Oncology Group performance status LT 2 (p = 0.095), and low/intermediate low International Prognostic Index (p = 0.076). In the female group and group of the patients without bulky tumor mass, treated with chemotherapeutic regimens including rituximab, methylation of p15 was significantly related to longer overall survival (p = 0.036 and 0.027, respectively). Our results suggest that promoter methylation of p15 gene could have prognostic value in DLBCL patients treated with rituximab when used in combination with gender and tumor size.
T2  - Clinical and Translational Science / CTS
T1  - Hypermethylation of p15 Gene in Diffuse - Large B-Cell Lymphoma: Association with Less Aggressiveness of the Disease
VL  - 7
IS  - 5
SP  - 384
EP  - 390
DO  - 10.1111/cts.12162
ER  - 

@article{
author = "Krajnović, Milena M. and Jovanovic, Maja Perunicic and Mihaljevic, Biljana and Andelic, Bosko and Tarabar, Olivera and Knežević-Ušaj, Slavica and Krtolica-Žikić, Koviljka",
year = "2014",
abstract = "In this study, methylation-specific polymerase chain reaction was used to investigate the potential prognostic significance of the methylation status of p15, p16, MGMT, and DAPK genes in 51 specimens of diffuse large B-cell lymphoma (DLBCL). Hypermethylation of p15 gene was significantly more prevalent in patients without relapse (p = 0.001) and there was a trend toward more frequent presence of p15 methylation in patients without death outcome within 5-year follow-up period (p = 0.086) Also, there was a trend toward accumulation of p15 methylation with favorable clinicopathological parameters including: age 60 years (p = 0.091), normal levels of lactate dehydrogenase (p = 0.090), Eastern Cooperative Oncology Group performance status LT 2 (p = 0.095), and low/intermediate low International Prognostic Index (p = 0.076). In the female group and group of the patients without bulky tumor mass, treated with chemotherapeutic regimens including rituximab, methylation of p15 was significantly related to longer overall survival (p = 0.036 and 0.027, respectively). Our results suggest that promoter methylation of p15 gene could have prognostic value in DLBCL patients treated with rituximab when used in combination with gender and tumor size.",
journal = "Clinical and Translational Science / CTS",
title = "Hypermethylation of p15 Gene in Diffuse - Large B-Cell Lymphoma: Association with Less Aggressiveness of the Disease",
volume = "7",
number = "5",
pages = "384-390",
doi = "10.1111/cts.12162"
}

Krajnović, M. M., Jovanovic, M. P., Mihaljevic, B., Andelic, B., Tarabar, O., Knežević-Ušaj, S.,& Krtolica-Žikić, K.. (2014). Hypermethylation of p15 Gene in Diffuse - Large B-Cell Lymphoma: Association with Less Aggressiveness of the Disease. in Clinical and Translational Science / CTS, 7(5), 384-390.
https://doi.org/10.1111/cts.12162

Krajnović MM, Jovanovic MP, Mihaljevic B, Andelic B, Tarabar O, Knežević-Ušaj S, Krtolica-Žikić K. Hypermethylation of p15 Gene in Diffuse - Large B-Cell Lymphoma: Association with Less Aggressiveness of the Disease. in Clinical and Translational Science / CTS. 2014;7(5):384-390.
doi:10.1111/cts.12162 .

Krajnović, Milena M., Jovanovic, Maja Perunicic, Mihaljevic, Biljana, Andelic, Bosko, Tarabar, Olivera, Knežević-Ušaj, Slavica, Krtolica-Žikić, Koviljka, "Hypermethylation of p15 Gene in Diffuse - Large B-Cell Lymphoma: Association with Less Aggressiveness of the Disease" in Clinical and Translational Science / CTS, 7, no. 5 (2014):384-390,
https://doi.org/10.1111/cts.12162 . .

TY  - JOUR
AU  - Krajnović, Milena M.
AU  - Radojkovic, Milica
AU  - Davidović, Radoslav S.
AU  - Dimitrijević, Bogomir B.
AU  - Krtolica-Žikić, Koviljka
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5388
AB  - In this study, methylation-specific polymerase chain reaction was used to investigate the role and potential prognostic significance of the methylation status of p16, p15, MGMT and DAPK genes in 32 specimens of follicular lymphoma (FL). Hypermethylation of p15 gene was associated with lower hemoglobin level (P = 0.020) and MGMT/DAPK comethylation with relapsed disease (P = 0.018). Among all patients with FL, there was no significant difference in the overall survival between those with hypermethylated and unmethylated of any examined genes. Therefore, we analyzed methylation in the different groups according to FL International Prognostic Index (FLIPI) and tumor grade. In the high-risk group, patients with hypermethylated p16 gene had significant lower overall survival than those with unmethylated p16 (P = 0.006) and trend toward shorter failure-free survival (P = 0.068). In the same risk group, there was a trend toward longer overall survival for patients with hypermethylated MGMT gene, compared to those with unmethylated MGMT gene (P = 0.066). p15 methylation had impact on shorter overall survival in grade I group of patients (P = 0.013), and DAPK methylation tended to have impact on shorter failure-free survival in the whole examined group (P = 0.079). Our results suggest that promotermethylation of p16 and MGMT genes could have prognostic value when used in combination with the FLIPI and p15 methylation in combination with tumor grade. Concurrent methylation of MGMT and DAPK genes could be the marker of tumor chemoresistance and disease recurrence.
T2  - Medical Oncology
T1  - Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma
VL  - 30
IS  - 1
DO  - 10.1007/s12032-012-0441-3
ER  - 

@article{
author = "Krajnović, Milena M. and Radojkovic, Milica and Davidović, Radoslav S. and Dimitrijević, Bogomir B. and Krtolica-Žikić, Koviljka",
year = "2013",
abstract = "In this study, methylation-specific polymerase chain reaction was used to investigate the role and potential prognostic significance of the methylation status of p16, p15, MGMT and DAPK genes in 32 specimens of follicular lymphoma (FL). Hypermethylation of p15 gene was associated with lower hemoglobin level (P = 0.020) and MGMT/DAPK comethylation with relapsed disease (P = 0.018). Among all patients with FL, there was no significant difference in the overall survival between those with hypermethylated and unmethylated of any examined genes. Therefore, we analyzed methylation in the different groups according to FL International Prognostic Index (FLIPI) and tumor grade. In the high-risk group, patients with hypermethylated p16 gene had significant lower overall survival than those with unmethylated p16 (P = 0.006) and trend toward shorter failure-free survival (P = 0.068). In the same risk group, there was a trend toward longer overall survival for patients with hypermethylated MGMT gene, compared to those with unmethylated MGMT gene (P = 0.066). p15 methylation had impact on shorter overall survival in grade I group of patients (P = 0.013), and DAPK methylation tended to have impact on shorter failure-free survival in the whole examined group (P = 0.079). Our results suggest that promotermethylation of p16 and MGMT genes could have prognostic value when used in combination with the FLIPI and p15 methylation in combination with tumor grade. Concurrent methylation of MGMT and DAPK genes could be the marker of tumor chemoresistance and disease recurrence.",
journal = "Medical Oncology",
title = "Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma",
volume = "30",
number = "1",
doi = "10.1007/s12032-012-0441-3"
}

Krajnović, M. M., Radojkovic, M., Davidović, R. S., Dimitrijević, B. B.,& Krtolica-Žikić, K.. (2013). Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma. in Medical Oncology, 30(1).
https://doi.org/10.1007/s12032-012-0441-3

Krajnović MM, Radojkovic M, Davidović RS, Dimitrijević BB, Krtolica-Žikić K. Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma. in Medical Oncology. 2013;30(1).
doi:10.1007/s12032-012-0441-3 .

Krajnović, Milena M., Radojkovic, Milica, Davidović, Radoslav S., Dimitrijević, Bogomir B., Krtolica-Žikić, Koviljka, "Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma" in Medical Oncology, 30, no. 1 (2013),
https://doi.org/10.1007/s12032-012-0441-3 . .

TY  - JOUR
AU  - Davidović, Radoslav S.
AU  - Sopta, Jelena
AU  - Mandušić, Vesna
AU  - Krajnović, Milena M.
AU  - Stanojevic, Maja
AU  - Tulic, Goran
AU  - Dimitrijević, Bogomir B.
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5646
AB  - Liposarcoma represents the most frequent group of soft tissue sarcomas. The group can be divided into three different classes: (1) differentiated/undifferentiated (WDLPS/DDLPS), (2) myxoid/round cell (MLPS/RCLPS) and (3) pleomorphic liposarcoma (PLS). It has become apparent that p53-p14 and Rb-p16 pathways play important roles in the pathogenesis of various sarcoma types. Molecular studies of the genes involved in these two pathways showed wide variations between the liposarcoma subtypes or even within the same subtype. We sought to examine mutational status of p53 and methylation status of p16(INK4a)/p14(ARF) genes in primary and recurrent liposarcoma tumors. There were twelve myxoid (12/18, 66.7 %) and six pleomorphic liposarcoma (6/18, 33.3 %) samples. Immunohistochemical analysis revealed that p53 protein was overexpressed in 3/12 MLPS (25 %) and 6/6 PLS (100 %). Mutational analysis showed that 2/11 MLPS (18.2 %) and 2/6 PLS (33.3 %) contained mutated p53 gene. On the other hand, 3/18 samples (16.7 %) had methylated p16 promoter. However, the frequencies of the p14(ARF) gene methylation were 83.3 % (10/12) and 50 % (3/6) in myxoid and pleomorphic group, respectively. Overall, 15 out of 18 (83.3 %) samples had either p53 gene mutation or methylated p14(ARF) promoter. The results from the current study suggest significant impact of the p14(ARF) gene methylation on the pathogenesis and progression of myxoid and to a lesser extent pleomorphic liposarcoma. Despite the limited number of samples, our study points to necessity of further investigation of p53-p14 and Rb-p16 pathways in liposarcoma.
T2  - Medical Oncology
T1  - p14(ARF) methylation is a common event in the pathogenesis and progression of myxoid and pleomorphic liposarcoma
VL  - 30
IS  - 3
DO  - 10.1007/s12032-013-0682-9
ER  - 

@article{
author = "Davidović, Radoslav S. and Sopta, Jelena and Mandušić, Vesna and Krajnović, Milena M. and Stanojevic, Maja and Tulic, Goran and Dimitrijević, Bogomir B.",
year = "2013",
abstract = "Liposarcoma represents the most frequent group of soft tissue sarcomas. The group can be divided into three different classes: (1) differentiated/undifferentiated (WDLPS/DDLPS), (2) myxoid/round cell (MLPS/RCLPS) and (3) pleomorphic liposarcoma (PLS). It has become apparent that p53-p14 and Rb-p16 pathways play important roles in the pathogenesis of various sarcoma types. Molecular studies of the genes involved in these two pathways showed wide variations between the liposarcoma subtypes or even within the same subtype. We sought to examine mutational status of p53 and methylation status of p16(INK4a)/p14(ARF) genes in primary and recurrent liposarcoma tumors. There were twelve myxoid (12/18, 66.7 %) and six pleomorphic liposarcoma (6/18, 33.3 %) samples. Immunohistochemical analysis revealed that p53 protein was overexpressed in 3/12 MLPS (25 %) and 6/6 PLS (100 %). Mutational analysis showed that 2/11 MLPS (18.2 %) and 2/6 PLS (33.3 %) contained mutated p53 gene. On the other hand, 3/18 samples (16.7 %) had methylated p16 promoter. However, the frequencies of the p14(ARF) gene methylation were 83.3 % (10/12) and 50 % (3/6) in myxoid and pleomorphic group, respectively. Overall, 15 out of 18 (83.3 %) samples had either p53 gene mutation or methylated p14(ARF) promoter. The results from the current study suggest significant impact of the p14(ARF) gene methylation on the pathogenesis and progression of myxoid and to a lesser extent pleomorphic liposarcoma. Despite the limited number of samples, our study points to necessity of further investigation of p53-p14 and Rb-p16 pathways in liposarcoma.",
journal = "Medical Oncology",
title = "p14(ARF) methylation is a common event in the pathogenesis and progression of myxoid and pleomorphic liposarcoma",
volume = "30",
number = "3",
doi = "10.1007/s12032-013-0682-9"
}

Davidović, R. S., Sopta, J., Mandušić, V., Krajnović, M. M., Stanojevic, M., Tulic, G.,& Dimitrijević, B. B.. (2013). p14(ARF) methylation is a common event in the pathogenesis and progression of myxoid and pleomorphic liposarcoma. in Medical Oncology, 30(3).
https://doi.org/10.1007/s12032-013-0682-9

Davidović RS, Sopta J, Mandušić V, Krajnović MM, Stanojevic M, Tulic G, Dimitrijević BB. p14(ARF) methylation is a common event in the pathogenesis and progression of myxoid and pleomorphic liposarcoma. in Medical Oncology. 2013;30(3).
doi:10.1007/s12032-013-0682-9 .

Davidović, Radoslav S., Sopta, Jelena, Mandušić, Vesna, Krajnović, Milena M., Stanojevic, Maja, Tulic, Goran, Dimitrijević, Bogomir B., "p14(ARF) methylation is a common event in the pathogenesis and progression of myxoid and pleomorphic liposarcoma" in Medical Oncology, 30, no. 3 (2013),
https://doi.org/10.1007/s12032-013-0682-9 . .

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

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

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

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

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

TY  - THES
AU  - Krajnović, Milena M.
PY  - 2013
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=806
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:7138/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024576946
UR  - http://nardus.mpn.gov.rs/123456789/2119
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7240
AB  - Difuzni B-krupnoćelijski limfom (DBKL) i folikularni limfom (FL), predstavljaju najučestalije entitete nehočkinovih limfoma i zajedno čine oko 50 % svih B-ćelijskih neoplazija. To su klinički i biološki heterogena oboljenja, sa visoko varijabilnim odgovorom na terapiju i uprkos značajnom napretku u terapiji, u velikom broju slučajeva ostaju neizlečiva. Aktuelni terapijski pristupi su praćeni brojnim neželjenim efektima i dovode do dugotrajne remisije i preživljavanja kod svega 50 % bolesnika. Najznačajniji klinički prediktor ishoda bolesti do danas je internacionalni prognostički indeks (IPI za DBKL, odnosno, FLIPI za FL), koji obuhvata odgovarajuće kliničke prognostičke parametre. Uprkos tome, oboleli koji pripadaju istim IPI/FLIPI kategorijama ispoljavaju značajne razlike u odgovoru na terapiju i preživljavanju, što ukazuje na postojanje značajne biološke heterogenosti u okviru svake IPI/FLIPI kategorije. Zbog toga je neophodno pronalaženje novih prognostičkih molekularnih parametara, koji bi omogućili precizniju podelu obolelih u grupe različitog stepena rizika i izbor odgovarajuće terapije. Primenom PCR metode specifične za metilaciju (MSP), ispitivan je metilacioni status p16, p15, MGMT i DAPK gena kod obolelih od DBKL i FL, kao bi se utvrdio njihov potencijalni prognostički značaj. Kod obolelih od DBKL, metilacija nijednog gena nije pokazala prognostički značaj, mada je uočena tendencija ka akumulaciji metilacije p15 gena kod ispitanika sa povoljnijim kliničko-patološkim karakteristikama. Kod obolelih od FL metilacija p16, p15 i MGMT gena bi mogla da ima određeni prognostički značaj, ukoliko se kombinuje sa FLIPI, gradusom tumora, odnosno starosnim dobom obolelihi. Istovremena metilacija MGMT i DAPK gena bi mogla da ukaže na grupu obolelih potencijalno hemorezistentnih na primenjenu hemoterapiju i sklonu recidivima bolesti.
AB  - Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most comon subgroups of non-Hodgkin’s lymphoma and comprise approximately 50 % of all cases. They represents clinically and biologically heterogeneous diseases, characterized with highly variable response to the treatment, and remain incurable despite the significant advances in therapy. Actual therapy regimens are agressive, and long-term remission and survival are ashieved in only 50 % of patients. The strongest clinical predictor of outcome to date in DLBCL and FL patients is the International Prognostic Index (IPI for DLBCL and FLIPI for FL) which includes several clinico-pathological prognostic parameters. However, patients with identical IPI/FLIPI still exhibit marked variability in survival, suggesting the presence of significant biological heterogenity within the same risk category. So, it is important to investigate additional molecular markers in order to further stratify patients into diferent risk groups, choose appropriate treatement strategy and improve prognosis. In this study, methylation-specific polymerase chain reaction (MSP) was used to investigate the role and potential prognostic significance of the methylation status of p16, p15, MGMT and DAPK genes in patients with DLBCL and FL. No one of four examined genes showed prognostic significance in patients with DLBCL, though we observed a tendency toward accumulation of p15 methylation with favorable clinico-pathological parameters. However, in patients with FL, our results suggest that promoter methylation of p16, p15 and MGMT genes could have some prognostic value when used in combination with the FLIPI, tumor grade and patients age, respectively. Concurrent methylation of MGMT and DAPK genes could be the marker of tumor chemoresistance and disease recurrence.
PB  - Универзитет у Београду, Биолошки факултет
T2  - Универзитет у Београду
T1  - Prognostički značaj aberantne metilacije CpG ostrvaca u folikularnim i difuznim B-krupnoćelijskim limfomima čoveka
T1  - Prognostic significance of aberrant CpG islands methylation in human follicular and diffuse large B-cell lymphoma
UR  - https://hdl.handle.net/21.15107/rcub_nardus_2119
ER  - 

@phdthesis{
author = "Krajnović, Milena M.",
year = "2013",
abstract = "Difuzni B-krupnoćelijski limfom (DBKL) i folikularni limfom (FL), predstavljaju najučestalije entitete nehočkinovih limfoma i zajedno čine oko 50 % svih B-ćelijskih neoplazija. To su klinički i biološki heterogena oboljenja, sa visoko varijabilnim odgovorom na terapiju i uprkos značajnom napretku u terapiji, u velikom broju slučajeva ostaju neizlečiva. Aktuelni terapijski pristupi su praćeni brojnim neželjenim efektima i dovode do dugotrajne remisije i preživljavanja kod svega 50 % bolesnika. Najznačajniji klinički prediktor ishoda bolesti do danas je internacionalni prognostički indeks (IPI za DBKL, odnosno, FLIPI za FL), koji obuhvata odgovarajuće kliničke prognostičke parametre. Uprkos tome, oboleli koji pripadaju istim IPI/FLIPI kategorijama ispoljavaju značajne razlike u odgovoru na terapiju i preživljavanju, što ukazuje na postojanje značajne biološke heterogenosti u okviru svake IPI/FLIPI kategorije. Zbog toga je neophodno pronalaženje novih prognostičkih molekularnih parametara, koji bi omogućili precizniju podelu obolelih u grupe različitog stepena rizika i izbor odgovarajuće terapije. Primenom PCR metode specifične za metilaciju (MSP), ispitivan je metilacioni status p16, p15, MGMT i DAPK gena kod obolelih od DBKL i FL, kao bi se utvrdio njihov potencijalni prognostički značaj. Kod obolelih od DBKL, metilacija nijednog gena nije pokazala prognostički značaj, mada je uočena tendencija ka akumulaciji metilacije p15 gena kod ispitanika sa povoljnijim kliničko-patološkim karakteristikama. Kod obolelih od FL metilacija p16, p15 i MGMT gena bi mogla da ima određeni prognostički značaj, ukoliko se kombinuje sa FLIPI, gradusom tumora, odnosno starosnim dobom obolelihi. Istovremena metilacija MGMT i DAPK gena bi mogla da ukaže na grupu obolelih potencijalno hemorezistentnih na primenjenu hemoterapiju i sklonu recidivima bolesti., Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most comon subgroups of non-Hodgkin’s lymphoma and comprise approximately 50 % of all cases. They represents clinically and biologically heterogeneous diseases, characterized with highly variable response to the treatment, and remain incurable despite the significant advances in therapy. Actual therapy regimens are agressive, and long-term remission and survival are ashieved in only 50 % of patients. The strongest clinical predictor of outcome to date in DLBCL and FL patients is the International Prognostic Index (IPI for DLBCL and FLIPI for FL) which includes several clinico-pathological prognostic parameters. However, patients with identical IPI/FLIPI still exhibit marked variability in survival, suggesting the presence of significant biological heterogenity within the same risk category. So, it is important to investigate additional molecular markers in order to further stratify patients into diferent risk groups, choose appropriate treatement strategy and improve prognosis. In this study, methylation-specific polymerase chain reaction (MSP) was used to investigate the role and potential prognostic significance of the methylation status of p16, p15, MGMT and DAPK genes in patients with DLBCL and FL. No one of four examined genes showed prognostic significance in patients with DLBCL, though we observed a tendency toward accumulation of p15 methylation with favorable clinico-pathological parameters. However, in patients with FL, our results suggest that promoter methylation of p16, p15 and MGMT genes could have some prognostic value when used in combination with the FLIPI, tumor grade and patients age, respectively. Concurrent methylation of MGMT and DAPK genes could be the marker of tumor chemoresistance and disease recurrence.",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Prognostički značaj aberantne metilacije CpG ostrvaca u folikularnim i difuznim B-krupnoćelijskim limfomima čoveka, Prognostic significance of aberrant CpG islands methylation in human follicular and diffuse large B-cell lymphoma",
url = "https://hdl.handle.net/21.15107/rcub_nardus_2119"
}

Krajnović, M. M.. (2013). Prognostički značaj aberantne metilacije CpG ostrvaca u folikularnim i difuznim B-krupnoćelijskim limfomima čoveka. in Универзитет у Београду
Универзитет у Београду, Биолошки факултет..
https://hdl.handle.net/21.15107/rcub_nardus_2119

Krajnović MM. Prognostički značaj aberantne metilacije CpG ostrvaca u folikularnim i difuznim B-krupnoćelijskim limfomima čoveka. in Универзитет у Београду. 2013;.
https://hdl.handle.net/21.15107/rcub_nardus_2119 .

Krajnović, Milena M., "Prognostički značaj aberantne metilacije CpG ostrvaca u folikularnim i difuznim B-krupnoćelijskim limfomima čoveka" in Универзитет у Београду (2013),
https://hdl.handle.net/21.15107/rcub_nardus_2119 .

TY  - JOUR
AU  - Kurtovic, Nada Kraguljac
AU  - Krajnović, Milena M.
AU  - Bogdanović, Andrija
AU  - Suvajdzic, Nada
AU  - Jovanović, Jelica
AU  - Dimitrijević, Bogomir B.
AU  - Čolović, Milica
AU  - Krtolica-Žikić, Koviljka
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5173
AB  - In this study, methylation-specific polymerase chain reaction (MS-PCR) was used to define the methylation status of the target promoter sequences of p15 and MGMT genes in the group of 21 adult patients with acute myeloid leukemia (AML). The incidence of aberrant hypermethylation of p15 gene (71 %) was higher comparing to MGMT gene (33 %), whereas concomitant methylation of both genes had 24 % of the patients. Although the incidence of cytogenetic abnormalities between the groups with a different methylation status of p15 and/or MGMT genes was not significantly different, we observed general trend of clustering of abnormalities with adverse prognosis into groups with concomitant hypermethylation of both genes and only p15 gene. Also, we showed that AML patients with concomitant methylation of p15/MGMT genes had a higher proportion of leukemic blast cells characterized with specific expression of individual leukocyte surface antigens (CD117(+)/CD7(+)/CD34(+)/CD15(-)), indicating leukemic cells as early myeloid progenitors. Although we could not prove that hypermethylation of p15 and/or MGMT genes is predictive parameter for response to therapy and overall survival, we noticed that AML patients with comethylated p15/MGMT genes or methylated p15 gene exhibited a higher frequency of early death, lower frequency of complete remissions as well as a trend for shorter overall survival. Assessing of the methylation status of p15 and MGMT genes may allow stratification of patients with AML into distinct groups with potentially different prognosis.
T2  - Medical Oncology
T1  - Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells
VL  - 29
IS  - 5
SP  - 3547
EP  - 3556
DO  - 10.1007/s12032-012-0289-6
ER  - 

@article{
author = "Kurtovic, Nada Kraguljac and Krajnović, Milena M. and Bogdanović, Andrija and Suvajdzic, Nada and Jovanović, Jelica and Dimitrijević, Bogomir B. and Čolović, Milica and Krtolica-Žikić, Koviljka",
year = "2012",
abstract = "In this study, methylation-specific polymerase chain reaction (MS-PCR) was used to define the methylation status of the target promoter sequences of p15 and MGMT genes in the group of 21 adult patients with acute myeloid leukemia (AML). The incidence of aberrant hypermethylation of p15 gene (71 %) was higher comparing to MGMT gene (33 %), whereas concomitant methylation of both genes had 24 % of the patients. Although the incidence of cytogenetic abnormalities between the groups with a different methylation status of p15 and/or MGMT genes was not significantly different, we observed general trend of clustering of abnormalities with adverse prognosis into groups with concomitant hypermethylation of both genes and only p15 gene. Also, we showed that AML patients with concomitant methylation of p15/MGMT genes had a higher proportion of leukemic blast cells characterized with specific expression of individual leukocyte surface antigens (CD117(+)/CD7(+)/CD34(+)/CD15(-)), indicating leukemic cells as early myeloid progenitors. Although we could not prove that hypermethylation of p15 and/or MGMT genes is predictive parameter for response to therapy and overall survival, we noticed that AML patients with comethylated p15/MGMT genes or methylated p15 gene exhibited a higher frequency of early death, lower frequency of complete remissions as well as a trend for shorter overall survival. Assessing of the methylation status of p15 and MGMT genes may allow stratification of patients with AML into distinct groups with potentially different prognosis.",
journal = "Medical Oncology",
title = "Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells",
volume = "29",
number = "5",
pages = "3547-3556",
doi = "10.1007/s12032-012-0289-6"
}

Kurtovic, N. K., Krajnović, M. M., Bogdanović, A., Suvajdzic, N., Jovanović, J., Dimitrijević, B. B., Čolović, M.,& Krtolica-Žikić, K.. (2012). Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells. in Medical Oncology, 29(5), 3547-3556.
https://doi.org/10.1007/s12032-012-0289-6

Kurtovic NK, Krajnović MM, Bogdanović A, Suvajdzic N, Jovanović J, Dimitrijević BB, Čolović M, Krtolica-Žikić K. Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells. in Medical Oncology. 2012;29(5):3547-3556.
doi:10.1007/s12032-012-0289-6 .

Kurtovic, Nada Kraguljac, Krajnović, Milena M., Bogdanović, Andrija, Suvajdzic, Nada, Jovanović, Jelica, Dimitrijević, Bogomir B., Čolović, Milica, Krtolica-Žikić, Koviljka, "Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells" in Medical Oncology, 29, no. 5 (2012):3547-3556,
https://doi.org/10.1007/s12032-012-0289-6 . .

TY  - CONF
AU  - Bogdanović, G.
AU  - Usaj-Knežević, S.
AU  - Krajnović, Milena M.
AU  - Kojić, Vesna
AU  - Nikin, Z.
AU  - Petrovic, T.
AU  - Krtolica-Žikić, Koviljka
AU  - Popsavin, M.
AU  - Krtolica, A.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/6991
C3  - European Journal of Cancer
T1  - Cellular and Molecular Characteristics of Novel Colon Cancer Cell Line
VL  - 48
SP  - S86
EP  - S86
DO  - 10.1016/S0959-8049(12)71043-2
ER  - 

@conference{
author = "Bogdanović, G. and Usaj-Knežević, S. and Krajnović, Milena M. and Kojić, Vesna and Nikin, Z. and Petrovic, T. and Krtolica-Žikić, Koviljka and Popsavin, M. and Krtolica, A.",
year = "2012",
journal = "European Journal of Cancer",
title = "Cellular and Molecular Characteristics of Novel Colon Cancer Cell Line",
volume = "48",
pages = "S86-S86",
doi = "10.1016/S0959-8049(12)71043-2"
}

Bogdanović, G., Usaj-Knežević, S., Krajnović, M. M., Kojić, V., Nikin, Z., Petrovic, T., Krtolica-Žikić, K., Popsavin, M.,& Krtolica, A.. (2012). Cellular and Molecular Characteristics of Novel Colon Cancer Cell Line. in European Journal of Cancer, 48, S86-S86.
https://doi.org/10.1016/S0959-8049(12)71043-2

Bogdanović G, Usaj-Knežević S, Krajnović MM, Kojić V, Nikin Z, Petrovic T, Krtolica-Žikić K, Popsavin M, Krtolica A. Cellular and Molecular Characteristics of Novel Colon Cancer Cell Line. in European Journal of Cancer. 2012;48:S86-S86.
doi:10.1016/S0959-8049(12)71043-2 .

Bogdanović, G., Usaj-Knežević, S., Krajnović, Milena M., Kojić, Vesna, Nikin, Z., Petrovic, T., Krtolica-Žikić, Koviljka, Popsavin, M., Krtolica, A., "Cellular and Molecular Characteristics of Novel Colon Cancer Cell Line" in European Journal of Cancer, 48 (2012):S86-S86,
https://doi.org/10.1016/S0959-8049(12)71043-2 . .

TY  - JOUR
AU  - Kurtovic, Nada Kraguljac
AU  - Krajnović, Milena M.
AU  - Dimitrijević, Bogomir B.
AU  - Mihaljevic, Biljana
AU  - Gotić, Mirjana
AU  - Krtolica-Žikić, Koviljka
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4045
AB  - The methylation status of the target promoter sequences of p15(INK4B) (p15) and O-6-methylguanine-DNA methyltransferase (MGMT) genes was studied by methylation-specific PCR in 10 adult patients with de novo B-cell non-Hodgkin lymphoma (B-NHL). The aberrant hypermethylation of the p15 gene was more frequent (50%) compared to the hypermethylation of the MGMT gene (30%), and was detected in different types of B-NHL in both genes. Hypermethylation of the MGMT gene occurred exclusively in association with the hypermethylation of the p15 gene. All lymphoma patients with hypermethylation of the p15 and/or MGMT genes had a higher clinical stage of the disease (IV - V). We show the association of anemia and/or thrombocytopenia with the hypermethylation of the p15 gene, ascribing the p15 gene as a potential prognostic marker in B-NHL. Comethylation of MGMT with the p15 gene represents a novel finding and presents both genes as candidates for future studies of the hypermethylation profiles of B-NHL.
T2  - Archives of Biological Sciences
T1  - Frequency of Aberrant Promoter Methylation of P15(Ink4b) and O-6-Methylguanine-Dna Methyltransferase Genes in B-Cell Non-Hodgkin Lymphoma: a Pilot Study
VL  - 62
IS  - 2
SP  - 211
EP  - 221
DO  - 10.2298/ABS1002211K
ER  - 

@article{
author = "Kurtovic, Nada Kraguljac and Krajnović, Milena M. and Dimitrijević, Bogomir B. and Mihaljevic, Biljana and Gotić, Mirjana and Krtolica-Žikić, Koviljka",
year = "2010",
abstract = "The methylation status of the target promoter sequences of p15(INK4B) (p15) and O-6-methylguanine-DNA methyltransferase (MGMT) genes was studied by methylation-specific PCR in 10 adult patients with de novo B-cell non-Hodgkin lymphoma (B-NHL). The aberrant hypermethylation of the p15 gene was more frequent (50%) compared to the hypermethylation of the MGMT gene (30%), and was detected in different types of B-NHL in both genes. Hypermethylation of the MGMT gene occurred exclusively in association with the hypermethylation of the p15 gene. All lymphoma patients with hypermethylation of the p15 and/or MGMT genes had a higher clinical stage of the disease (IV - V). We show the association of anemia and/or thrombocytopenia with the hypermethylation of the p15 gene, ascribing the p15 gene as a potential prognostic marker in B-NHL. Comethylation of MGMT with the p15 gene represents a novel finding and presents both genes as candidates for future studies of the hypermethylation profiles of B-NHL.",
journal = "Archives of Biological Sciences",
title = "Frequency of Aberrant Promoter Methylation of P15(Ink4b) and O-6-Methylguanine-Dna Methyltransferase Genes in B-Cell Non-Hodgkin Lymphoma: a Pilot Study",
volume = "62",
number = "2",
pages = "211-221",
doi = "10.2298/ABS1002211K"
}

Kurtovic, N. K., Krajnović, M. M., Dimitrijević, B. B., Mihaljevic, B., Gotić, M.,& Krtolica-Žikić, K.. (2010). Frequency of Aberrant Promoter Methylation of P15(Ink4b) and O-6-Methylguanine-Dna Methyltransferase Genes in B-Cell Non-Hodgkin Lymphoma: a Pilot Study. in Archives of Biological Sciences, 62(2), 211-221.
https://doi.org/10.2298/ABS1002211K

Kurtovic NK, Krajnović MM, Dimitrijević BB, Mihaljevic B, Gotić M, Krtolica-Žikić K. Frequency of Aberrant Promoter Methylation of P15(Ink4b) and O-6-Methylguanine-Dna Methyltransferase Genes in B-Cell Non-Hodgkin Lymphoma: a Pilot Study. in Archives of Biological Sciences. 2010;62(2):211-221.
doi:10.2298/ABS1002211K .

Kurtovic, Nada Kraguljac, Krajnović, Milena M., Dimitrijević, Bogomir B., Mihaljevic, Biljana, Gotić, Mirjana, Krtolica-Žikić, Koviljka, "Frequency of Aberrant Promoter Methylation of P15(Ink4b) and O-6-Methylguanine-Dna Methyltransferase Genes in B-Cell Non-Hodgkin Lymphoma: a Pilot Study" in Archives of Biological Sciences, 62, no. 2 (2010):211-221,
https://doi.org/10.2298/ABS1002211K . .

TY  - JOUR
AU  - Krtolica-Žikić, Koviljka
AU  - Krajnović, Milena M.
AU  - Usaj-Knežević, Slavica
AU  - Babić, Dragan
AU  - Jovanovic, Dusan
AU  - Dimitrijević, Bogomir B.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3184
AB  - AIM: To investigate the significance of p16 and O-6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCS, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P LT 0.05, chi(2)-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 +/- 6.0 mo vs 23.1 +/- 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P LT 0.001, chi(2)-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 +/- 1.9 mo vs 37.0 +/- 1.8 mo, P LT 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis. (C) 2007 The WJG Press. All rights reserved.
T2  - World Journal of Gastroenterology
T1  - Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value
VL  - 13
IS  - 8
SP  - 1187
EP  - 1194
DO  - 10.3748/wjg.v13.i8.1187
ER  - 

@article{
author = "Krtolica-Žikić, Koviljka and Krajnović, Milena M. and Usaj-Knežević, Slavica and Babić, Dragan and Jovanovic, Dusan and Dimitrijević, Bogomir B.",
year = "2007",
abstract = "AIM: To investigate the significance of p16 and O-6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCS, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P LT 0.05, chi(2)-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 +/- 6.0 mo vs 23.1 +/- 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P LT 0.001, chi(2)-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 +/- 1.9 mo vs 37.0 +/- 1.8 mo, P LT 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis. (C) 2007 The WJG Press. All rights reserved.",
journal = "World Journal of Gastroenterology",
title = "Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value",
volume = "13",
number = "8",
pages = "1187-1194",
doi = "10.3748/wjg.v13.i8.1187"
}

Krtolica-Žikić, K., Krajnović, M. M., Usaj-Knežević, S., Babić, D., Jovanovic, D.,& Dimitrijević, B. B.. (2007). Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value. in World Journal of Gastroenterology, 13(8), 1187-1194.
https://doi.org/10.3748/wjg.v13.i8.1187

Krtolica-Žikić K, Krajnović MM, Usaj-Knežević S, Babić D, Jovanovic D, Dimitrijević BB. Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value. in World Journal of Gastroenterology. 2007;13(8):1187-1194.
doi:10.3748/wjg.v13.i8.1187 .

Krtolica-Žikić, Koviljka, Krajnović, Milena M., Usaj-Knežević, Slavica, Babić, Dragan, Jovanovic, Dusan, Dimitrijević, Bogomir B., "Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value" in World Journal of Gastroenterology, 13, no. 8 (2007):1187-1194,
https://doi.org/10.3748/wjg.v13.i8.1187 . .

TY  - JOUR
AU  - Bogdanović, Gordana
AU  - Jurišić, Vladimir
AU  - Kraguljac, Nada
AU  - Mrđanović, Jasminka Ž.
AU  - Jakimov, Dimitar
AU  - Krtolica-Žikić, Koviljka
AU  - Krajnović, Milena M.
AU  - Magic, Zvonko
AU  - Stojiljković, Bratislav
AU  - Andrijevic, Ljiljana
AU  - Srdić, Tatjana
AU  - Baltic, Mirjana
AU  - Popovic, Stevan
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3219
AB  - We report on characteristics of the first human cell line, PC-MDS, derived from a bone marrow of a patient with therapy-related myelodysplastic syndrome (t-MDS) who had no overt post-MDS leukemia. Classic cytology analyses, immunophenotyping, cytogenetic and molecular genetic procedures were used for characterization of the cell line. PC-MDS cells are positive for the expression of CD13, CD15, CD30, CD33, and CD45 antigen. Positive cytochemical staining and immunophenotype analyses indicated that PC-MDS cells have some characteristics of the early myeloid precursor cell. The karyotype analysis of PC-MDS cell line revealed various numerical and structural changes including those typically associated with t-MDS: del(5)(q13)[7], der(5)t(5;11)(p11;q11)[13], -7[6], del(7)(q31)[2], +20[3], -20[4]. Evaluation of methylation status in a promoter region of p 15, p 16 and MGMT genes showed biallelic hypermethylation pattern of 5 promoter region only in MGMT gene. PC-MDS is the first t-MDS derived cell line, and based on its immunological, cytogenetic and molecular characterization could be a new tool in evaluation of complex biology of MDS and a model for methylation studies. (c) 2007 Elsevier Ltd. All rights reserved.
T2  - Leukemia Research
T1  - Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome
VL  - 31
IS  - 8
SP  - 1097
EP  - 1105
DO  - 10.1016/j.leukres.2007.01.012
ER  - 

@article{
author = "Bogdanović, Gordana and Jurišić, Vladimir and Kraguljac, Nada and Mrđanović, Jasminka Ž. and Jakimov, Dimitar and Krtolica-Žikić, Koviljka and Krajnović, Milena M. and Magic, Zvonko and Stojiljković, Bratislav and Andrijevic, Ljiljana and Srdić, Tatjana and Baltic, Mirjana and Popovic, Stevan",
year = "2007",
abstract = "We report on characteristics of the first human cell line, PC-MDS, derived from a bone marrow of a patient with therapy-related myelodysplastic syndrome (t-MDS) who had no overt post-MDS leukemia. Classic cytology analyses, immunophenotyping, cytogenetic and molecular genetic procedures were used for characterization of the cell line. PC-MDS cells are positive for the expression of CD13, CD15, CD30, CD33, and CD45 antigen. Positive cytochemical staining and immunophenotype analyses indicated that PC-MDS cells have some characteristics of the early myeloid precursor cell. The karyotype analysis of PC-MDS cell line revealed various numerical and structural changes including those typically associated with t-MDS: del(5)(q13)[7], der(5)t(5;11)(p11;q11)[13], -7[6], del(7)(q31)[2], +20[3], -20[4]. Evaluation of methylation status in a promoter region of p 15, p 16 and MGMT genes showed biallelic hypermethylation pattern of 5 promoter region only in MGMT gene. PC-MDS is the first t-MDS derived cell line, and based on its immunological, cytogenetic and molecular characterization could be a new tool in evaluation of complex biology of MDS and a model for methylation studies. (c) 2007 Elsevier Ltd. All rights reserved.",
journal = "Leukemia Research",
title = "Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome",
volume = "31",
number = "8",
pages = "1097-1105",
doi = "10.1016/j.leukres.2007.01.012"
}

Bogdanović, G., Jurišić, V., Kraguljac, N., Mrđanović, J. Ž., Jakimov, D., Krtolica-Žikić, K., Krajnović, M. M., Magic, Z., Stojiljković, B., Andrijevic, L., Srdić, T., Baltic, M.,& Popovic, S.. (2007). Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome. in Leukemia Research, 31(8), 1097-1105.
https://doi.org/10.1016/j.leukres.2007.01.012

Bogdanović G, Jurišić V, Kraguljac N, Mrđanović JŽ, Jakimov D, Krtolica-Žikić K, Krajnović MM, Magic Z, Stojiljković B, Andrijevic L, Srdić T, Baltic M, Popovic S. Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome. in Leukemia Research. 2007;31(8):1097-1105.
doi:10.1016/j.leukres.2007.01.012 .

Bogdanović, Gordana, Jurišić, Vladimir, Kraguljac, Nada, Mrđanović, Jasminka Ž., Jakimov, Dimitar, Krtolica-Žikić, Koviljka, Krajnović, Milena M., Magic, Zvonko, Stojiljković, Bratislav, Andrijevic, Ljiljana, Srdić, Tatjana, Baltic, Mirjana, Popovic, Stevan, "Characteristics of novel myeloid precursor cell line, PC-MDS, established from a bone marrow of the patient with therapy-related myelodysplastic syndrome" in Leukemia Research, 31, no. 8 (2007):1097-1105,
https://doi.org/10.1016/j.leukres.2007.01.012 . .