TY  - JOUR
AU  - Rosić, Jovana
AU  - Miladinov, Marko
AU  - Dragičević, Sandra
AU  - Erić, Katarina
AU  - Bogdanović, Aleksandar
AU  - Krivokapić, Zoran
AU  - Nikolić, Aleksandra
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1769
AB  - Considering the impact of SMAD7 deregulation in colorectal cancer (CRC) progression and the
significance of single nucleotide variant (SNV)-mediated disruptions of microRNA (miRNA)-dependent regulation
for cancer susceptibility, our study aimed to analyze genetic variation in the SMAD7 3′ untranslated region (
3′UTR) in CRC, measure differences in allelic mRNA expression, and evaluate its interference with miRNAmediated
post-transcriptional regulation.
Patients and Methods: This study included 80 patients with different CRC stages and six human colon cancer cell
lines of various histological origins. SMAD7 3′ UTR was analyzed by direct sequencing, followed by the relative
quantification of differential allelic expression of detected variants by allele-specific qRT-PCR. In silico tools were
employed for predictions of regulatory consequences of detected variants.
Results: A total of four different SNVs in one cell line and nine patients were found, among which were a novel
somatic point variant and three already known germline variants (rs16950113, rs1050799536, and
rs1043778717). All evaluated SNVs exhibited variable extents of allelic imbalance in expression. In silico analysis
predicted significant effects of SNVs on miRNA binding efficiency, with each SNV disrupting existing and
creating new target sites for one or more miRNAs.
Conclusion: Imbalance observed in the expression of SNV alleles altering miRNA binding suggests that all
investigated SNVs are potential contributing factors impacting SMAD7 expression regulation in CRC that further
studies should investigate.
PB  - Elsevier
T2  - Gene
T1  - Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance
SP  - 147217
VL  - 859
DO  - doi.org/10.1016/j.gene.2023.147217
ER  - 

@article{
author = "Rosić, Jovana and Miladinov, Marko and Dragičević, Sandra and Erić, Katarina and Bogdanović, Aleksandar and Krivokapić, Zoran and Nikolić, Aleksandra",
year = "2023",
abstract = "Considering the impact of SMAD7 deregulation in colorectal cancer (CRC) progression and the
significance of single nucleotide variant (SNV)-mediated disruptions of microRNA (miRNA)-dependent regulation
for cancer susceptibility, our study aimed to analyze genetic variation in the SMAD7 3′ untranslated region (
3′UTR) in CRC, measure differences in allelic mRNA expression, and evaluate its interference with miRNAmediated
post-transcriptional regulation.
Patients and Methods: This study included 80 patients with different CRC stages and six human colon cancer cell
lines of various histological origins. SMAD7 3′ UTR was analyzed by direct sequencing, followed by the relative
quantification of differential allelic expression of detected variants by allele-specific qRT-PCR. In silico tools were
employed for predictions of regulatory consequences of detected variants.
Results: A total of four different SNVs in one cell line and nine patients were found, among which were a novel
somatic point variant and three already known germline variants (rs16950113, rs1050799536, and
rs1043778717). All evaluated SNVs exhibited variable extents of allelic imbalance in expression. In silico analysis
predicted significant effects of SNVs on miRNA binding efficiency, with each SNV disrupting existing and
creating new target sites for one or more miRNAs.
Conclusion: Imbalance observed in the expression of SNV alleles altering miRNA binding suggests that all
investigated SNVs are potential contributing factors impacting SMAD7 expression regulation in CRC that further
studies should investigate.",
publisher = "Elsevier",
journal = "Gene",
title = "Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance",
pages = "147217",
volume = "859",
doi = "doi.org/10.1016/j.gene.2023.147217"
}

Rosić, J., Miladinov, M., Dragičević, S., Erić, K., Bogdanović, A., Krivokapić, Z.,& Nikolić, A.. (2023). Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance. in Gene
Elsevier., 859, 147217.
https://doi.org/doi.org/10.1016/j.gene.2023.147217

Rosić J, Miladinov M, Dragičević S, Erić K, Bogdanović A, Krivokapić Z, Nikolić A. Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance. in Gene. 2023;859:147217.
doi:doi.org/10.1016/j.gene.2023.147217 .

Rosić, Jovana, Miladinov, Marko, Dragičević, Sandra, Erić, Katarina, Bogdanović, Aleksandar, Krivokapić, Zoran, Nikolić, Aleksandra, "Genetic analysis and allele-specific expression of SMAD7 3′UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance" in Gene, 859 (2023):147217,
https://doi.org/doi.org/10.1016/j.gene.2023.147217 . .

TY  - CONF
AU  - Erić, K.
AU  - Miladinov, Marko
AU  - Dragičević, Sandra
AU  - Rosić, Jovana
AU  - Krivokapić, Zoran
AU  - Zeljić, Katarina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2083
AB  - Background & objectives: Long non coding RNA, H19 is an imprinted, maternally expressed gene, usually deregulated in diferent cancer types, including rectal cancer. This study aimed to investigate H19 role as a potential biomarker to predict therapy response in rectal cancer patients. Methods: The study included 14 patients diagnosed with rectal cancer, treated with neoadjuvant chemoradio therapy (nCRT). RNA was isolated by TRIzol reagent from samples of rectal cancer tissue  before and after nCRT. Relative expression of H19 was normal- ized to housekeeping GAPDH gene, and expression was analysed  by quantitative real-time PCR. Relative expression of H19 was calculated by 2-ΔCt method. Results: Relative expression of H19 was significantly increased in rectal cancer tissue after nCRT (0.244±0.408) compared to the tissue before nCRT (0.043±0.055), p=0.004, Wilcoxon test. According to tumour regression grade (TRG), 85.71% (12/14) of  patients did not respond, while 14.28% (2/14) responded to pre- operative CRT. Responders (TRG1, TRG2) and non-responders  (TRG3, TRG4) did not differ in H19 expression in tumour tissue before (p=0.659, Mann-Whitney U test) as well as after nCRT  (p=0.999, Mann-Whitney U test). Receiver operating curve analy- sis indicates that H19 expression in colorectal tissue before nCRT  can not be used as a biomarker for distinguishing responders from non-responders (AUC=0.625, 95%CI=0.257-0.992, p=0.583).  Conclusion: Our study suggests H19 upregulation upon neoadju- vant chemoradiotherapy in rectal cancer. The potential predictive  value of H19 as a biomarker of therapy response should be studied in a larger group of patients.
PB  - Springer
C3  - Virchows Archiv, 34 th European Congress of Pathology - Abstracts
T1  - Long non-coding RNA H19 expression in rectal cancer and therapy response
EP  - S145
IS  - Supplement 1
SP  - S145
SP  - PS-15-017
VL  - 481
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2083
ER  - 

@conference{
author = "Erić, K. and Miladinov, Marko and Dragičević, Sandra and Rosić, Jovana and Krivokapić, Zoran and Zeljić, Katarina",
year = "2022",
abstract = "Background & objectives: Long non coding RNA, H19 is an imprinted, maternally expressed gene, usually deregulated in diferent cancer types, including rectal cancer. This study aimed to investigate H19 role as a potential biomarker to predict therapy response in rectal cancer patients. Methods: The study included 14 patients diagnosed with rectal cancer, treated with neoadjuvant chemoradio therapy (nCRT). RNA was isolated by TRIzol reagent from samples of rectal cancer tissue  before and after nCRT. Relative expression of H19 was normal- ized to housekeeping GAPDH gene, and expression was analysed  by quantitative real-time PCR. Relative expression of H19 was calculated by 2-ΔCt method. Results: Relative expression of H19 was significantly increased in rectal cancer tissue after nCRT (0.244±0.408) compared to the tissue before nCRT (0.043±0.055), p=0.004, Wilcoxon test. According to tumour regression grade (TRG), 85.71% (12/14) of  patients did not respond, while 14.28% (2/14) responded to pre- operative CRT. Responders (TRG1, TRG2) and non-responders  (TRG3, TRG4) did not differ in H19 expression in tumour tissue before (p=0.659, Mann-Whitney U test) as well as after nCRT  (p=0.999, Mann-Whitney U test). Receiver operating curve analy- sis indicates that H19 expression in colorectal tissue before nCRT  can not be used as a biomarker for distinguishing responders from non-responders (AUC=0.625, 95%CI=0.257-0.992, p=0.583).  Conclusion: Our study suggests H19 upregulation upon neoadju- vant chemoradiotherapy in rectal cancer. The potential predictive  value of H19 as a biomarker of therapy response should be studied in a larger group of patients.",
publisher = "Springer",
journal = "Virchows Archiv, 34 th European Congress of Pathology - Abstracts",
title = "Long non-coding RNA H19 expression in rectal cancer and therapy response",
pages = "S145-S145-PS-15-017",
number = "Supplement 1",
volume = "481",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2083"
}

Erić, K., Miladinov, M., Dragičević, S., Rosić, J., Krivokapić, Z.,& Zeljić, K.. (2022). Long non-coding RNA H19 expression in rectal cancer and therapy response. in Virchows Archiv, 34 th European Congress of Pathology - Abstracts
Springer., 481(Supplement 1), S145-S145.
https://hdl.handle.net/21.15107/rcub_imagine_2083

Erić K, Miladinov M, Dragičević S, Rosić J, Krivokapić Z, Zeljić K. Long non-coding RNA H19 expression in rectal cancer and therapy response. in Virchows Archiv, 34 th European Congress of Pathology - Abstracts. 2022;481(Supplement 1):S145-S145.
https://hdl.handle.net/21.15107/rcub_imagine_2083 .

Erić, K., Miladinov, Marko, Dragičević, Sandra, Rosić, Jovana, Krivokapić, Zoran, Zeljić, Katarina, "Long non-coding RNA H19 expression in rectal cancer and therapy response" in Virchows Archiv, 34 th European Congress of Pathology - Abstracts, 481, no. Supplement 1 (2022):S145-S145,
https://hdl.handle.net/21.15107/rcub_imagine_2083 .

TY  - JOUR
AU  - Despotović, Jovana
AU  - Bogdanović, Aleksandar
AU  - Dragičević, Sandra
AU  - Galun, Danijel
AU  - Krivokapić, Zoran
AU  - Nikolić, Aleksandra
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1588
AB  - This study aimed to examine the expression pattern of tumoral and circulating miR-93-5p in patients with colorectal cancer (CRC) liver metastasis (CRLM) and to explore its predictive and prognostic potential. CRLM tissue, surrounding non-tumor liver tissue, and serum were obtained from 35 patients with CRLM. The expression pattern of tissue and circulating miR-93-5p in patients with CRLM was determined using quantitative polymerase chain reaction, using miR-16-5p for normalization. Sample-based cut-off values for CRLM and serum miR-93-5p expression were calculated using Receiver Operating Characteristic curve analysis to stratify the patients into high and low miR-93-5p expression groups which were that compared with patients??? clinicopathological data, therapy response, one-year disease-free survival, and disease recurrence. Relative miR-93-5p expression was higher in CRLM in comparison to the non-metastatic liver tissue (p lt 0.001). CRLM miR-93-5p expression showed moderate negative correlation with carcinoembryonic antigen levels (r=???0.406; p=0.016). There were no differences in high-/low-miR-93-5p expression and therapy responders vs. non-responders, which was confirmed in vitro using metastatic and normal colonic cells SW620 and HCEC-1CT, respectively. No difference was observed in one-year recurrence-free survival in patients with high vs. low miR-93-5p expression in CRLM or serum. However, high miR-93-5p serum levels were significantly associated with early disease recurrence (p=0.035). In conclusion, miR-93-5p serum levels could be potentially used as a prognostic factor for early disease recurrence in CRLM patients.
PB  - Aepress Sro, Bratislava
T2  - Neoplasma
T1  - Prognostic potential of circulating miR-93-5p in patients with colorectal cancer liver metastases
EP  - 442
IS  - 2
SP  - 430
VL  - 69
DO  - 10.4149/neo_2021_210603N749
ER  - 

@article{
author = "Despotović, Jovana and Bogdanović, Aleksandar and Dragičević, Sandra and Galun, Danijel and Krivokapić, Zoran and Nikolić, Aleksandra",
year = "2022",
abstract = "This study aimed to examine the expression pattern of tumoral and circulating miR-93-5p in patients with colorectal cancer (CRC) liver metastasis (CRLM) and to explore its predictive and prognostic potential. CRLM tissue, surrounding non-tumor liver tissue, and serum were obtained from 35 patients with CRLM. The expression pattern of tissue and circulating miR-93-5p in patients with CRLM was determined using quantitative polymerase chain reaction, using miR-16-5p for normalization. Sample-based cut-off values for CRLM and serum miR-93-5p expression were calculated using Receiver Operating Characteristic curve analysis to stratify the patients into high and low miR-93-5p expression groups which were that compared with patients??? clinicopathological data, therapy response, one-year disease-free survival, and disease recurrence. Relative miR-93-5p expression was higher in CRLM in comparison to the non-metastatic liver tissue (p lt 0.001). CRLM miR-93-5p expression showed moderate negative correlation with carcinoembryonic antigen levels (r=???0.406; p=0.016). There were no differences in high-/low-miR-93-5p expression and therapy responders vs. non-responders, which was confirmed in vitro using metastatic and normal colonic cells SW620 and HCEC-1CT, respectively. No difference was observed in one-year recurrence-free survival in patients with high vs. low miR-93-5p expression in CRLM or serum. However, high miR-93-5p serum levels were significantly associated with early disease recurrence (p=0.035). In conclusion, miR-93-5p serum levels could be potentially used as a prognostic factor for early disease recurrence in CRLM patients.",
publisher = "Aepress Sro, Bratislava",
journal = "Neoplasma",
title = "Prognostic potential of circulating miR-93-5p in patients with colorectal cancer liver metastases",
pages = "442-430",
number = "2",
volume = "69",
doi = "10.4149/neo_2021_210603N749"
}

Despotović, J., Bogdanović, A., Dragičević, S., Galun, D., Krivokapić, Z.,& Nikolić, A.. (2022). Prognostic potential of circulating miR-93-5p in patients with colorectal cancer liver metastases. in Neoplasma
Aepress Sro, Bratislava., 69(2), 430-442.
https://doi.org/10.4149/neo_2021_210603N749

Despotović J, Bogdanović A, Dragičević S, Galun D, Krivokapić Z, Nikolić A. Prognostic potential of circulating miR-93-5p in patients with colorectal cancer liver metastases. in Neoplasma. 2022;69(2):430-442.
doi:10.4149/neo_2021_210603N749 .

Despotović, Jovana, Bogdanović, Aleksandar, Dragičević, Sandra, Galun, Danijel, Krivokapić, Zoran, Nikolić, Aleksandra, "Prognostic potential of circulating miR-93-5p in patients with colorectal cancer liver metastases" in Neoplasma, 69, no. 2 (2022):430-442,
https://doi.org/10.4149/neo_2021_210603N749 . .

TY  - JOUR
AU  - Babić, Tamara
AU  - Dragičević, Sandra
AU  - Miladinov, Marko
AU  - Krivokapić, Zoran
AU  - Nikolić, Aleksandra
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1532
AB  - Background: Transcripts with alternative 5'-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, thus executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. The aim of this study was to investigate the relative abundance of the transcript SMAD4-201 in colorectal cell lines and tissues in order to establish if its fluctuations may be associated with colorectal cancer (CRC). Methods: Relative abundance of SMAD4-201 in total SMAD4 mRNA was analyzed using quantitative PCR in a set of permanent human colon cell lines and tumor and corresponding healthy tissue samples from patients with CRC. Results: The relative abundance of SMAD4-201 in analyzed cell lines varied between 16 and 47%. A similar relative abundance of SMAD4-201 transcript was found in the majority of analyzed human tumor tissue samples, and it was averagely 20% lower in non-malignant in comparison to malignant tissue samples (p = 0.001). Transcript SMAD4-202 was not detectable in any of the analyzed samples, so the observed fluctuations in the composition of SMAD4 transcripts can be attributed to transcripts other than SMAD4-201 and SMAD4-202. Conclusion: The expression profile of SMAD4-201 in human tumor and non-tumor tissue samples may indicate the translational potential of this molecule in CRC, but further research is needed to clarify its usability as a potential biomarker for early diagnosis.
PB  - BMC, London
T2  - Bmc Cancer
T1  - SMAD4-201 transcript as a putative biomarker in colorectal cancer
IS  - 1
VL  - 22
DO  - 10.1186/s12885-022-09186-z
ER  - 

@article{
author = "Babić, Tamara and Dragičević, Sandra and Miladinov, Marko and Krivokapić, Zoran and Nikolić, Aleksandra",
year = "2022",
abstract = "Background: Transcripts with alternative 5'-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, thus executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. The aim of this study was to investigate the relative abundance of the transcript SMAD4-201 in colorectal cell lines and tissues in order to establish if its fluctuations may be associated with colorectal cancer (CRC). Methods: Relative abundance of SMAD4-201 in total SMAD4 mRNA was analyzed using quantitative PCR in a set of permanent human colon cell lines and tumor and corresponding healthy tissue samples from patients with CRC. Results: The relative abundance of SMAD4-201 in analyzed cell lines varied between 16 and 47%. A similar relative abundance of SMAD4-201 transcript was found in the majority of analyzed human tumor tissue samples, and it was averagely 20% lower in non-malignant in comparison to malignant tissue samples (p = 0.001). Transcript SMAD4-202 was not detectable in any of the analyzed samples, so the observed fluctuations in the composition of SMAD4 transcripts can be attributed to transcripts other than SMAD4-201 and SMAD4-202. Conclusion: The expression profile of SMAD4-201 in human tumor and non-tumor tissue samples may indicate the translational potential of this molecule in CRC, but further research is needed to clarify its usability as a potential biomarker for early diagnosis.",
publisher = "BMC, London",
journal = "Bmc Cancer",
title = "SMAD4-201 transcript as a putative biomarker in colorectal cancer",
number = "1",
volume = "22",
doi = "10.1186/s12885-022-09186-z"
}

Babić, T., Dragičević, S., Miladinov, M., Krivokapić, Z.,& Nikolić, A.. (2022). SMAD4-201 transcript as a putative biomarker in colorectal cancer. in Bmc Cancer
BMC, London., 22(1).
https://doi.org/10.1186/s12885-022-09186-z

Babić T, Dragičević S, Miladinov M, Krivokapić Z, Nikolić A. SMAD4-201 transcript as a putative biomarker in colorectal cancer. in Bmc Cancer. 2022;22(1).
doi:10.1186/s12885-022-09186-z .

Babić, Tamara, Dragičević, Sandra, Miladinov, Marko, Krivokapić, Zoran, Nikolić, Aleksandra, "SMAD4-201 transcript as a putative biomarker in colorectal cancer" in Bmc Cancer, 22, no. 1 (2022),
https://doi.org/10.1186/s12885-022-09186-z . .

TY  - JOUR
AU  - Nikolić, Aleksandra
AU  - Despotović, Jovana
AU  - Babić, Tamara
AU  - Antić, Jadranka
AU  - Marković, Srdjan
AU  - Krivokapić, Zoran
AU  - Radojković, Dragica
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1595
AB  - In colorectal cancer (CRC), inactivation of SMAD4 occurs early in the disease development and SMAD4 represents one of key driver genes in progression and metastasis. Loss of SMAD4 protein expression is a relatively common feature of sporadic colorectal cancers, and it was observed to be even more frequent in tumors of patients with early onset disease and also more frequent in microsatellite stable tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain in colorectal cancer patients with early onset disease and microsatellite stable tumors. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients. The study was conducted in a selected set of DNA samples extracted from the tumors of CRC patients who had less than 50 years at the time of diagnosis. Genetic analysis of C-terminal domain has encompassed analysis of exons 9, 10, 11 and 12 of the SMAD4 gene by PCR and direct DNA sequencing. Among the twenty analyzed tumor DNAs, one sample was found to harbor a SMAD4 variant: NC_000018.9:g.48591918C  gt  T; (NM005359.5: c.1081C  gt  T; Arg361Cys). The variant was discovered in exon 9, affecting the codon 361, which represents a mutational hot spot within the SMAD4 gene. This variant was discovered in homozygous state in the tumor of a 47 yr old female with T3 stage carcinoma of the right colon. Considering the incidence and functional consequences of SMAD4 exon 9 variants, the screening of this region could be a useful low cost strategy for the genetic analysis of colorectal tumors from patients with early onset disease, as well as for susceptibility testing.
PB  - Pleiades Publishing Inc, New York
T2  - Cytology and Genetics
T1  - SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study
EP  - 276
IS  - 3
SP  - 273
VL  - 56
DO  - 10.3103/S0095452722030082
ER  - 

@article{
author = "Nikolić, Aleksandra and Despotović, Jovana and Babić, Tamara and Antić, Jadranka and Marković, Srdjan and Krivokapić, Zoran and Radojković, Dragica",
year = "2022",
abstract = "In colorectal cancer (CRC), inactivation of SMAD4 occurs early in the disease development and SMAD4 represents one of key driver genes in progression and metastasis. Loss of SMAD4 protein expression is a relatively common feature of sporadic colorectal cancers, and it was observed to be even more frequent in tumors of patients with early onset disease and also more frequent in microsatellite stable tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain in colorectal cancer patients with early onset disease and microsatellite stable tumors. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients. The study was conducted in a selected set of DNA samples extracted from the tumors of CRC patients who had less than 50 years at the time of diagnosis. Genetic analysis of C-terminal domain has encompassed analysis of exons 9, 10, 11 and 12 of the SMAD4 gene by PCR and direct DNA sequencing. Among the twenty analyzed tumor DNAs, one sample was found to harbor a SMAD4 variant: NC_000018.9:g.48591918C  gt  T; (NM005359.5: c.1081C  gt  T; Arg361Cys). The variant was discovered in exon 9, affecting the codon 361, which represents a mutational hot spot within the SMAD4 gene. This variant was discovered in homozygous state in the tumor of a 47 yr old female with T3 stage carcinoma of the right colon. Considering the incidence and functional consequences of SMAD4 exon 9 variants, the screening of this region could be a useful low cost strategy for the genetic analysis of colorectal tumors from patients with early onset disease, as well as for susceptibility testing.",
publisher = "Pleiades Publishing Inc, New York",
journal = "Cytology and Genetics",
title = "SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study",
pages = "276-273",
number = "3",
volume = "56",
doi = "10.3103/S0095452722030082"
}

Nikolić, A., Despotović, J., Babić, T., Antić, J., Marković, S., Krivokapić, Z.,& Radojković, D.. (2022). SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study. in Cytology and Genetics
Pleiades Publishing Inc, New York., 56(3), 273-276.
https://doi.org/10.3103/S0095452722030082

Nikolić A, Despotović J, Babić T, Antić J, Marković S, Krivokapić Z, Radojković D. SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study. in Cytology and Genetics. 2022;56(3):273-276.
doi:10.3103/S0095452722030082 .

Nikolić, Aleksandra, Despotović, Jovana, Babić, Tamara, Antić, Jadranka, Marković, Srdjan, Krivokapić, Zoran, Radojković, Dragica, "SMAD4 Gene Analysis in Patients with Early Onset Colorectal Cancer: A Pilot Study" in Cytology and Genetics, 56, no. 3 (2022):273-276,
https://doi.org/10.3103/S0095452722030082 . .

TY  - JOUR
AU  - Nikolić, Aleksandra
AU  - Krivokapić, Zoran
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1562
AB  - The progress that has been made in the treatment of rectal cancer has mostly resulted from multimodality strategy approach that combines surgery, chemotherapy and radiotherapy. In locally advanced rectal cancer (LARC), surgery remains the primary treatment, while neoadjuvant chemoradiotherapy (nCRT) is used to downsize or downstage the tumor before surgical resection. Highly variable response to nCRT observed in LARC patients raises the need for biomarkers to enable prediction and evaluation of treatment response in a more efficient and timely manner than currently available tools. The search for predictive biomarkers continues beyond blood proteins, which have failed in subsequent validation studies. This review presents nucleic acids based markers and their predictive potential in LARC patients. Most of the candidate biomarkers come from relatively small single-institution studies. The only candidate biomarker that emerged as relevant in more than a single study was elevated levels of Fusobacterium nucleatum nucleic acids in tumor tissue. Considering that this marker is easily accessible through non-invasive analysis of faecal samples, its predictive potential is worth further validation. The other candidate nucleic acid-based biomarkers require more consistent studies on larger cohorts before they can be considered for use in clinical setting.
PB  - Elsevier Sci Ltd, Oxford
T2  - Surgical Oncology-Oxford
T1  - Nucleic acid-based markers of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
VL  - 41
DO  - 10.1016/j.suronc.2022.101743
ER  - 

@article{
author = "Nikolić, Aleksandra and Krivokapić, Zoran",
year = "2022",
abstract = "The progress that has been made in the treatment of rectal cancer has mostly resulted from multimodality strategy approach that combines surgery, chemotherapy and radiotherapy. In locally advanced rectal cancer (LARC), surgery remains the primary treatment, while neoadjuvant chemoradiotherapy (nCRT) is used to downsize or downstage the tumor before surgical resection. Highly variable response to nCRT observed in LARC patients raises the need for biomarkers to enable prediction and evaluation of treatment response in a more efficient and timely manner than currently available tools. The search for predictive biomarkers continues beyond blood proteins, which have failed in subsequent validation studies. This review presents nucleic acids based markers and their predictive potential in LARC patients. Most of the candidate biomarkers come from relatively small single-institution studies. The only candidate biomarker that emerged as relevant in more than a single study was elevated levels of Fusobacterium nucleatum nucleic acids in tumor tissue. Considering that this marker is easily accessible through non-invasive analysis of faecal samples, its predictive potential is worth further validation. The other candidate nucleic acid-based biomarkers require more consistent studies on larger cohorts before they can be considered for use in clinical setting.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Surgical Oncology-Oxford",
title = "Nucleic acid-based markers of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer",
volume = "41",
doi = "10.1016/j.suronc.2022.101743"
}

Nikolić, A.,& Krivokapić, Z.. (2022). Nucleic acid-based markers of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. in Surgical Oncology-Oxford
Elsevier Sci Ltd, Oxford., 41.
https://doi.org/10.1016/j.suronc.2022.101743

Nikolić A, Krivokapić Z. Nucleic acid-based markers of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. in Surgical Oncology-Oxford. 2022;41.
doi:10.1016/j.suronc.2022.101743 .

Nikolić, Aleksandra, Krivokapić, Zoran, "Nucleic acid-based markers of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer" in Surgical Oncology-Oxford, 41 (2022),
https://doi.org/10.1016/j.suronc.2022.101743 . .

TY  - CONF
AU  - Babić, Tamara
AU  - Dragičević, Sandra
AU  - Miladinov, Marko
AU  - Krivokapić, Zoran
AU  - Nikolić, Aleksandra
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1563
PB  - Springernature, London
C3  - European Journal of Human Genetics
T1  - SMAD4 gene coding transcripts with alternative 5 ' ends as colorectal cancer biomarkers
EP  - 556
IS  - SUPPL 1
SP  - 556
VL  - 30
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1563
ER  - 

@conference{
author = "Babić, Tamara and Dragičević, Sandra and Miladinov, Marko and Krivokapić, Zoran and Nikolić, Aleksandra",
year = "2022",
publisher = "Springernature, London",
journal = "European Journal of Human Genetics",
title = "SMAD4 gene coding transcripts with alternative 5 ' ends as colorectal cancer biomarkers",
pages = "556-556",
number = "SUPPL 1",
volume = "30",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1563"
}

Babić, T., Dragičević, S., Miladinov, M., Krivokapić, Z.,& Nikolić, A.. (2022). SMAD4 gene coding transcripts with alternative 5 ' ends as colorectal cancer biomarkers. in European Journal of Human Genetics
Springernature, London., 30(SUPPL 1), 556-556.
https://hdl.handle.net/21.15107/rcub_imagine_1563

Babić T, Dragičević S, Miladinov M, Krivokapić Z, Nikolić A. SMAD4 gene coding transcripts with alternative 5 ' ends as colorectal cancer biomarkers. in European Journal of Human Genetics. 2022;30(SUPPL 1):556-556.
https://hdl.handle.net/21.15107/rcub_imagine_1563 .

Babić, Tamara, Dragičević, Sandra, Miladinov, Marko, Krivokapić, Zoran, Nikolić, Aleksandra, "SMAD4 gene coding transcripts with alternative 5 ' ends as colorectal cancer biomarkers" in European Journal of Human Genetics, 30, no. SUPPL 1 (2022):556-556,
https://hdl.handle.net/21.15107/rcub_imagine_1563 .

TY  - JOUR
AU  - Babić, Tamara
AU  - Lygirou, Vasiliki
AU  - Rosić, Jovana
AU  - Miladinov, Marko
AU  - Rom, Aleksandra Djikic
AU  - Baira, Eirini
AU  - Stroggilos, Rafael
AU  - Pappa, Eftychia
AU  - Zoidakis, Jerome
AU  - Krivokapić, Zoran
AU  - Nikolić, Aleksandra
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1521
AB  - Purpose In the search for candidate predictive biomarkers to evaluate response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, only a few studies report proteomic profiles of tumor tissue before and after nCRT. The aim of our study was to determine differentially expressed proteins between responders and non-responders before and after the therapy in order to identify candidate molecules for prediction and follow-up of response to nCRT. Experimental Design The study has included tissue sections of rectal tumor and non-tumor mucosa from five responders and five non-responders taken before and after nCRT from patients with locally advanced rectal cancer. Extracted proteins were analyzed by LC-MS/MS analysis followed by a set of bioinformatics analyses. Result Proteomics analysis provided a mean of approximately 1050 protein identifications per sample. A comparison of proteomic profiles between responders and non-responders has identified 18 differentially expressed proteins. Pathway analysis demonstrated high metabolic activity in non-responders' tumors before nCRT, indicating the presence of intrinsic chemoradioresistance in these subjects. Two proteins associated with poor prognosis in colorectal cancer, ADAM10 and CAD, were identified as candidate predictive biomarkers as they were present in non-responders only. Conclusions and Clinical Relevance Shortlisted proteins from our study should be further validated as candidate biomarkers for response to routinely applied nCRT protocols.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Proteomics Clinical Applications
T1  - Pilot proteomic study of locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy indicates high metabolic activity in non-responders' tumor tissue
DO  - 10.1002/prca.202100116
ER  - 

@article{
author = "Babić, Tamara and Lygirou, Vasiliki and Rosić, Jovana and Miladinov, Marko and Rom, Aleksandra Djikic and Baira, Eirini and Stroggilos, Rafael and Pappa, Eftychia and Zoidakis, Jerome and Krivokapić, Zoran and Nikolić, Aleksandra",
year = "2022",
abstract = "Purpose In the search for candidate predictive biomarkers to evaluate response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, only a few studies report proteomic profiles of tumor tissue before and after nCRT. The aim of our study was to determine differentially expressed proteins between responders and non-responders before and after the therapy in order to identify candidate molecules for prediction and follow-up of response to nCRT. Experimental Design The study has included tissue sections of rectal tumor and non-tumor mucosa from five responders and five non-responders taken before and after nCRT from patients with locally advanced rectal cancer. Extracted proteins were analyzed by LC-MS/MS analysis followed by a set of bioinformatics analyses. Result Proteomics analysis provided a mean of approximately 1050 protein identifications per sample. A comparison of proteomic profiles between responders and non-responders has identified 18 differentially expressed proteins. Pathway analysis demonstrated high metabolic activity in non-responders' tumors before nCRT, indicating the presence of intrinsic chemoradioresistance in these subjects. Two proteins associated with poor prognosis in colorectal cancer, ADAM10 and CAD, were identified as candidate predictive biomarkers as they were present in non-responders only. Conclusions and Clinical Relevance Shortlisted proteins from our study should be further validated as candidate biomarkers for response to routinely applied nCRT protocols.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Proteomics Clinical Applications",
title = "Pilot proteomic study of locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy indicates high metabolic activity in non-responders' tumor tissue",
doi = "10.1002/prca.202100116"
}

Babić, T., Lygirou, V., Rosić, J., Miladinov, M., Rom, A. D., Baira, E., Stroggilos, R., Pappa, E., Zoidakis, J., Krivokapić, Z.,& Nikolić, A.. (2022). Pilot proteomic study of locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy indicates high metabolic activity in non-responders' tumor tissue. in Proteomics Clinical Applications
Wiley-V C H Verlag Gmbh, Weinheim..
https://doi.org/10.1002/prca.202100116

Babić T, Lygirou V, Rosić J, Miladinov M, Rom AD, Baira E, Stroggilos R, Pappa E, Zoidakis J, Krivokapić Z, Nikolić A. Pilot proteomic study of locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy indicates high metabolic activity in non-responders' tumor tissue. in Proteomics Clinical Applications. 2022;.
doi:10.1002/prca.202100116 .

Babić, Tamara, Lygirou, Vasiliki, Rosić, Jovana, Miladinov, Marko, Rom, Aleksandra Djikic, Baira, Eirini, Stroggilos, Rafael, Pappa, Eftychia, Zoidakis, Jerome, Krivokapić, Zoran, Nikolić, Aleksandra, "Pilot proteomic study of locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy indicates high metabolic activity in non-responders' tumor tissue" in Proteomics Clinical Applications (2022),
https://doi.org/10.1002/prca.202100116 . .

TY  - JOUR
AU  - Bogdanović, Aleksandar
AU  - Despotović, Jovana
AU  - Galun, Danijel
AU  - Bidzić, Nemanja
AU  - Nikolić, Aleksandra
AU  - Rosić, Jovana
AU  - Krivokapić, Zoran
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1490
AB  - Purpose: There are limited data on expression of epithelial-mesenchymal transition (EMT) markers in patients with colorectal liver metastases (CRLM). The study aim was to evaluate the expression and prognostic significance of E-cadherin (CDH1), fibronectin (FN1) and vimentin (VIM) in patients with CRLM after curative-intent liver resection. Patients and Methods: Thirty patients with CRLM managed by curative-intent liver resection were included in this prospective pilot study. Blood samples, colorectal liver metastases and surrounding non-tumor liver tissue were collected. Expression of CDH1, FN1 and VIM was analyzed by quantitative real-time polymerase chain reaction. Expression in CRLM and non-tumor liver tissue was compared, while expression in serum was correlated with CRLM expression. One-year recurrence-free survival was compared between patients with low and high CDH1, FN1 and VIM expression. Results: The expression of CDH1 was similar in CRLM and non-tumor liver tissues, while FN1 and VIM expression was significantly lower in metastatic tissue (P=0.003 and pP lt  0.001, respectively). Serum expression of CDH1 and VIM was detected in 66.7% and 93.3% of patients, respectively, while FN1 was not detected in any of the patients. The correlation of CDH1 and VIM expression between CRLM and serum was not statistically significant. Decreased CDH1 expression in CRLM and decreased VIM expression in serum were associated with early recurrence after surgical treatment of CRLM. Conclusion: Lower expression of CDH1 in CRLM and lower serum expression of VIM were found to be associated with early recurrence after liver resection for CRLM.
PB  - Dove Medical Press Ltd, Albany
T2  - Cancer Management and Research
T1  - Prognostic Significance of CDH1, FN1 and VIM for Early Recurrence in Patients with Colorectal Liver Metastasis After Liver Resection
EP  - 171
SP  - 163
VL  - 13
DO  - 10.2147/CMAR.S287974
ER  - 

@article{
author = "Bogdanović, Aleksandar and Despotović, Jovana and Galun, Danijel and Bidzić, Nemanja and Nikolić, Aleksandra and Rosić, Jovana and Krivokapić, Zoran",
year = "2021",
abstract = "Purpose: There are limited data on expression of epithelial-mesenchymal transition (EMT) markers in patients with colorectal liver metastases (CRLM). The study aim was to evaluate the expression and prognostic significance of E-cadherin (CDH1), fibronectin (FN1) and vimentin (VIM) in patients with CRLM after curative-intent liver resection. Patients and Methods: Thirty patients with CRLM managed by curative-intent liver resection were included in this prospective pilot study. Blood samples, colorectal liver metastases and surrounding non-tumor liver tissue were collected. Expression of CDH1, FN1 and VIM was analyzed by quantitative real-time polymerase chain reaction. Expression in CRLM and non-tumor liver tissue was compared, while expression in serum was correlated with CRLM expression. One-year recurrence-free survival was compared between patients with low and high CDH1, FN1 and VIM expression. Results: The expression of CDH1 was similar in CRLM and non-tumor liver tissues, while FN1 and VIM expression was significantly lower in metastatic tissue (P=0.003 and pP lt  0.001, respectively). Serum expression of CDH1 and VIM was detected in 66.7% and 93.3% of patients, respectively, while FN1 was not detected in any of the patients. The correlation of CDH1 and VIM expression between CRLM and serum was not statistically significant. Decreased CDH1 expression in CRLM and decreased VIM expression in serum were associated with early recurrence after surgical treatment of CRLM. Conclusion: Lower expression of CDH1 in CRLM and lower serum expression of VIM were found to be associated with early recurrence after liver resection for CRLM.",
publisher = "Dove Medical Press Ltd, Albany",
journal = "Cancer Management and Research",
title = "Prognostic Significance of CDH1, FN1 and VIM for Early Recurrence in Patients with Colorectal Liver Metastasis After Liver Resection",
pages = "171-163",
volume = "13",
doi = "10.2147/CMAR.S287974"
}

Bogdanović, A., Despotović, J., Galun, D., Bidzić, N., Nikolić, A., Rosić, J.,& Krivokapić, Z.. (2021). Prognostic Significance of CDH1, FN1 and VIM for Early Recurrence in Patients with Colorectal Liver Metastasis After Liver Resection. in Cancer Management and Research
Dove Medical Press Ltd, Albany., 13, 163-171.
https://doi.org/10.2147/CMAR.S287974

Bogdanović A, Despotović J, Galun D, Bidzić N, Nikolić A, Rosić J, Krivokapić Z. Prognostic Significance of CDH1, FN1 and VIM for Early Recurrence in Patients with Colorectal Liver Metastasis After Liver Resection. in Cancer Management and Research. 2021;13:163-171.
doi:10.2147/CMAR.S287974 .

Bogdanović, Aleksandar, Despotović, Jovana, Galun, Danijel, Bidzić, Nemanja, Nikolić, Aleksandra, Rosić, Jovana, Krivokapić, Zoran, "Prognostic Significance of CDH1, FN1 and VIM for Early Recurrence in Patients with Colorectal Liver Metastasis After Liver Resection" in Cancer Management and Research, 13 (2021):163-171,
https://doi.org/10.2147/CMAR.S287974 . .

TY  - JOUR
AU  - Prosenc-Zmrzljak, Ursula
AU  - Kosir, Rok
AU  - Krivokapić, Zoran
AU  - Radojković, Dragica
AU  - Nikolić, Aleksandra
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1494
AB  - Liquid biopsy and cell-free DNA (cfDNA) show great promise in cancer diagnostics. In this study, we designed a custom droplet digital PCR (ddPCR) assay for the quantification and quality control of cfDNA isolated from serum. The assay was validated on a group of locally advanced colorectal cancer (CRC) patients and two control groups-patients with hemorrhoids and healthy individuals. The assay shows a high correlation with Qubit measurement (r = 0.976) but offers a higher dynamic range. Mean concentrations of cfDNA were 12.36 ng/mu L, 5.17 ng/mu L, and 0.29 ng/mu L for CRC, hemorrhoid patients, and healthy controls, respectively. The quality of cfDNA was assessed with the measurement of B-cell DNA contamination. On a subset of CRC patients, we compared the mutation status on KRAS (G12A, G12D, G12V, G13D) and BRAF (V600E) genes in the primary tumor and cfDNA isolated from the serum. A total of 70.6% of primary tumor samples were mutated, and the mean fractional abundance of mutations was 9.50%. The matching serum samples were mutated in 38% cases with an average fractional abundance of 0.23%. We conclude that any decisions based solely on the amount of cfDNA present in patient serum must be interpreted carefully and in the context of co-morbidities. This study explores the potential of ddPCR somatic mutations detection from liquid biopsy as a supplement to tissue biopsy in targeted personalized CRC patient management.
PB  - MDPI, Basel
T2  - Genes
T1  - Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients
IS  - 2
VL  - 12
DO  - 10.3390/genes12020289
ER  - 

@article{
author = "Prosenc-Zmrzljak, Ursula and Kosir, Rok and Krivokapić, Zoran and Radojković, Dragica and Nikolić, Aleksandra",
year = "2021",
abstract = "Liquid biopsy and cell-free DNA (cfDNA) show great promise in cancer diagnostics. In this study, we designed a custom droplet digital PCR (ddPCR) assay for the quantification and quality control of cfDNA isolated from serum. The assay was validated on a group of locally advanced colorectal cancer (CRC) patients and two control groups-patients with hemorrhoids and healthy individuals. The assay shows a high correlation with Qubit measurement (r = 0.976) but offers a higher dynamic range. Mean concentrations of cfDNA were 12.36 ng/mu L, 5.17 ng/mu L, and 0.29 ng/mu L for CRC, hemorrhoid patients, and healthy controls, respectively. The quality of cfDNA was assessed with the measurement of B-cell DNA contamination. On a subset of CRC patients, we compared the mutation status on KRAS (G12A, G12D, G12V, G13D) and BRAF (V600E) genes in the primary tumor and cfDNA isolated from the serum. A total of 70.6% of primary tumor samples were mutated, and the mean fractional abundance of mutations was 9.50%. The matching serum samples were mutated in 38% cases with an average fractional abundance of 0.23%. We conclude that any decisions based solely on the amount of cfDNA present in patient serum must be interpreted carefully and in the context of co-morbidities. This study explores the potential of ddPCR somatic mutations detection from liquid biopsy as a supplement to tissue biopsy in targeted personalized CRC patient management.",
publisher = "MDPI, Basel",
journal = "Genes",
title = "Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients",
number = "2",
volume = "12",
doi = "10.3390/genes12020289"
}

Prosenc-Zmrzljak, U., Kosir, R., Krivokapić, Z., Radojković, D.,& Nikolić, A.. (2021). Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients. in Genes
MDPI, Basel., 12(2).
https://doi.org/10.3390/genes12020289

Prosenc-Zmrzljak U, Kosir R, Krivokapić Z, Radojković D, Nikolić A. Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients. in Genes. 2021;12(2).
doi:10.3390/genes12020289 .

Prosenc-Zmrzljak, Ursula, Kosir, Rok, Krivokapić, Zoran, Radojković, Dragica, Nikolić, Aleksandra, "Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients" in Genes, 12, no. 2 (2021),
https://doi.org/10.3390/genes12020289 . .

TY  - CONF
AU  - Despotović, Jovana
AU  - Babić, Tamara
AU  - Krivokapić, Zoran
AU  - Nikolić, Aleksandra
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1801
UR  - https://fightcolorectalcancer.org/blog/recap-rally-on-research-eao-crc/
AB  - SMAD4 protein loss is a relatively common feature of sporadic
colorectal cancers (CRC), and it was observed to be even more frequent in early-age onset CRC
patients and microsatellite stable (MSS) tumors. Pathogenic variants in the SMAD4 gene are
usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The
aim of this study was to perform genetic analysis of SMAD4 C-terminal domain of MSS early-age
onset CRC patients. This pilot study was conducted with a purpose of investigating if such genetic
screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC
patients.
PB  - Fight Colorectal Cancer (Fight CRC)
C3  - Fight Colorectal Cancer (Fight CRC)
T1  - Genetic analysis of SMAD4 C-terminal domain in patients with microsatellite stable early- age onset colorectal cancer
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1801
ER  - 

@conference{
author = "Despotović, Jovana and Babić, Tamara and Krivokapić, Zoran and Nikolić, Aleksandra",
year = "2021",
abstract = "SMAD4 protein loss is a relatively common feature of sporadic
colorectal cancers (CRC), and it was observed to be even more frequent in early-age onset CRC
patients and microsatellite stable (MSS) tumors. Pathogenic variants in the SMAD4 gene are
usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The
aim of this study was to perform genetic analysis of SMAD4 C-terminal domain of MSS early-age
onset CRC patients. This pilot study was conducted with a purpose of investigating if such genetic
screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC
patients.",
publisher = "Fight Colorectal Cancer (Fight CRC)",
journal = "Fight Colorectal Cancer (Fight CRC)",
title = "Genetic analysis of SMAD4 C-terminal domain in patients with microsatellite stable early- age onset colorectal cancer",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1801"
}

Despotović, J., Babić, T., Krivokapić, Z.,& Nikolić, A.. (2021). Genetic analysis of SMAD4 C-terminal domain in patients with microsatellite stable early- age onset colorectal cancer. in Fight Colorectal Cancer (Fight CRC)
Fight Colorectal Cancer (Fight CRC)..
https://hdl.handle.net/21.15107/rcub_imagine_1801

Despotović J, Babić T, Krivokapić Z, Nikolić A. Genetic analysis of SMAD4 C-terminal domain in patients with microsatellite stable early- age onset colorectal cancer. in Fight Colorectal Cancer (Fight CRC). 2021;.
https://hdl.handle.net/21.15107/rcub_imagine_1801 .

Despotović, Jovana, Babić, Tamara, Krivokapić, Zoran, Nikolić, Aleksandra, "Genetic analysis of SMAD4 C-terminal domain in patients with microsatellite stable early- age onset colorectal cancer" in Fight Colorectal Cancer (Fight CRC) (2021),
https://hdl.handle.net/21.15107/rcub_imagine_1801 .

TY  - JOUR
AU  - Rosić, Jovana
AU  - Dragičević, Sandra
AU  - Miladinov, Marko
AU  - Despotović, Jovana
AU  - Bogdanović, Aleksandar
AU  - Krivokapić, Zoran
AU  - Nikolić, Aleksandra
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1469
AB  - Inhibitory SMAD7 and common mediator SMAD4 play crucial roles in SMAD-dependent TGF-I3 signaling that is often disrupted in colorectal cancer (CRC). This study aimed to profile the expression of SMAD7 and SMAD4 in primary and metastatic CRC and to evaluate their significance in disease progression and therapy response. The expression of SMAD7 and SMAD4 genes was analyzed by quantitative real-time PCR in tissues from 35 primary and metastatic CRC patients and in vitro in 7 human cell lines originating from colon tissue. Expression levels of SMAD7 and SMAD4, as well as their ratio, were determined and their association with tumor characteristics and response to therapy were evaluated. SMAD4 level was significantly lower in tumors compared to non-tumor tissues in both primary (p = 0.001) and metastatic (p = 0.001) CRC patients, while tumor expression of SMAD7 was significantly lower from non-tumor tissue only in metastatic patients (p = 0.017). SMAD7/SMAD4 ratio was elevated in CRC primary tumor tissues and cell lines compared to corresponding non-tumor tissues and cell line, respectively (p = 0.003). SMAD7 expression was significantly elevated in primary tumor tissues obtained from responders to neoadjuvant chemoradiotherapy (nCRT) compared to non-responders (p = 0.014). Alterations of expression and ratio of SMAD7 and SMAD4 in CRC cell lines, primary rectal cancer, and liver metastasis emphasize the importance of these genes in different stages of disease progression. Differential expression of SMAD7 in responders versus non-responders to nCRT should be further investigated for its potential predictive value.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Experimental and Molecular Pathology
T1  - SMAD7 and SMAD4 expression in colorectal cancer progression and therapy response
VL  - 123
DO  - 10.1016/j.yexmp.2021.104714
ER  - 

@article{
author = "Rosić, Jovana and Dragičević, Sandra and Miladinov, Marko and Despotović, Jovana and Bogdanović, Aleksandar and Krivokapić, Zoran and Nikolić, Aleksandra",
year = "2021",
abstract = "Inhibitory SMAD7 and common mediator SMAD4 play crucial roles in SMAD-dependent TGF-I3 signaling that is often disrupted in colorectal cancer (CRC). This study aimed to profile the expression of SMAD7 and SMAD4 in primary and metastatic CRC and to evaluate their significance in disease progression and therapy response. The expression of SMAD7 and SMAD4 genes was analyzed by quantitative real-time PCR in tissues from 35 primary and metastatic CRC patients and in vitro in 7 human cell lines originating from colon tissue. Expression levels of SMAD7 and SMAD4, as well as their ratio, were determined and their association with tumor characteristics and response to therapy were evaluated. SMAD4 level was significantly lower in tumors compared to non-tumor tissues in both primary (p = 0.001) and metastatic (p = 0.001) CRC patients, while tumor expression of SMAD7 was significantly lower from non-tumor tissue only in metastatic patients (p = 0.017). SMAD7/SMAD4 ratio was elevated in CRC primary tumor tissues and cell lines compared to corresponding non-tumor tissues and cell line, respectively (p = 0.003). SMAD7 expression was significantly elevated in primary tumor tissues obtained from responders to neoadjuvant chemoradiotherapy (nCRT) compared to non-responders (p = 0.014). Alterations of expression and ratio of SMAD7 and SMAD4 in CRC cell lines, primary rectal cancer, and liver metastasis emphasize the importance of these genes in different stages of disease progression. Differential expression of SMAD7 in responders versus non-responders to nCRT should be further investigated for its potential predictive value.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Experimental and Molecular Pathology",
title = "SMAD7 and SMAD4 expression in colorectal cancer progression and therapy response",
volume = "123",
doi = "10.1016/j.yexmp.2021.104714"
}

Rosić, J., Dragičević, S., Miladinov, M., Despotović, J., Bogdanović, A., Krivokapić, Z.,& Nikolić, A.. (2021). SMAD7 and SMAD4 expression in colorectal cancer progression and therapy response. in Experimental and Molecular Pathology
Academic Press Inc Elsevier Science, San Diego., 123.
https://doi.org/10.1016/j.yexmp.2021.104714

Rosić J, Dragičević S, Miladinov M, Despotović J, Bogdanović A, Krivokapić Z, Nikolić A. SMAD7 and SMAD4 expression in colorectal cancer progression and therapy response. in Experimental and Molecular Pathology. 2021;123.
doi:10.1016/j.yexmp.2021.104714 .

Rosić, Jovana, Dragičević, Sandra, Miladinov, Marko, Despotović, Jovana, Bogdanović, Aleksandar, Krivokapić, Zoran, Nikolić, Aleksandra, "SMAD7 and SMAD4 expression in colorectal cancer progression and therapy response" in Experimental and Molecular Pathology, 123 (2021),
https://doi.org/10.1016/j.yexmp.2021.104714 . .

TY  - JOUR
AU  - Petrović-Sunderić, Jelena
AU  - Dragičević, Sandra
AU  - Krnjajić, Mina
AU  - Ristanović, Momcilo
AU  - Nikolić, Aleksandra
AU  - Krivokapić, Zoran
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1115
AB  - Purpose: The RAD51 gene plays an important role in homologous strand exchange in DNA repair. Two common single nucleotide polymorphisms in this gene, 135G  gt  C and 172G  gt  T, were associated with altered gene transcription. While 135G  gt  C was already linked to breast and colorectal cancers in certain populations, 172G  gt  T is far less investigated, although sporadic studies showed it could be a prognostic factor for some cancer lesions. The purpose of this study was to investigate RAD51 172G  gt  T polymorphism in Serbian population, its association with colorectal carcinoma, as well as correlation with disease characteristics and response to neoadjuvant chemoradiotherapy. Methods: The 172G  gt  T polymorphism was evaluated by PCR-RFLP method in blood samples of 209 colorectal cancer patients and 43 healthy subjects who served as controls. The distribution of genotypes was also analyzed in respect to several tumor characteristics in cases where histopathological data were available. Results: A significant association between the RAD51 172G  gt  T polymoprhism and desmoplastic reaction of colorectal cancer was demonstrated. The 172G allele was found to be significantly more frequent in patients with more intensive desmoplastic response of the tumor tissue. Conclusions: The results of our study suggest that the 172T allele of RAD51 may be a favorable prognostic factor in Serbian patients with colorectal cancer, although larger prospective studies are required to confirm this finding.
PB  - Balkan Union of Oncology (B.U.ON.)
T2  - Journal of Buon
T1  - Polymorphism RAD51 172G > T in Serbian patients with colorectal cancer
EP  - 940
IS  - 4
SP  - 936
VL  - 23
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1115
ER  - 

@article{
author = "Petrović-Sunderić, Jelena and Dragičević, Sandra and Krnjajić, Mina and Ristanović, Momcilo and Nikolić, Aleksandra and Krivokapić, Zoran",
year = "2018",
abstract = "Purpose: The RAD51 gene plays an important role in homologous strand exchange in DNA repair. Two common single nucleotide polymorphisms in this gene, 135G  gt  C and 172G  gt  T, were associated with altered gene transcription. While 135G  gt  C was already linked to breast and colorectal cancers in certain populations, 172G  gt  T is far less investigated, although sporadic studies showed it could be a prognostic factor for some cancer lesions. The purpose of this study was to investigate RAD51 172G  gt  T polymorphism in Serbian population, its association with colorectal carcinoma, as well as correlation with disease characteristics and response to neoadjuvant chemoradiotherapy. Methods: The 172G  gt  T polymorphism was evaluated by PCR-RFLP method in blood samples of 209 colorectal cancer patients and 43 healthy subjects who served as controls. The distribution of genotypes was also analyzed in respect to several tumor characteristics in cases where histopathological data were available. Results: A significant association between the RAD51 172G  gt  T polymoprhism and desmoplastic reaction of colorectal cancer was demonstrated. The 172G allele was found to be significantly more frequent in patients with more intensive desmoplastic response of the tumor tissue. Conclusions: The results of our study suggest that the 172T allele of RAD51 may be a favorable prognostic factor in Serbian patients with colorectal cancer, although larger prospective studies are required to confirm this finding.",
publisher = "Balkan Union of Oncology (B.U.ON.)",
journal = "Journal of Buon",
title = "Polymorphism RAD51 172G > T in Serbian patients with colorectal cancer",
pages = "940-936",
number = "4",
volume = "23",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1115"
}

Petrović-Sunderić, J., Dragičević, S., Krnjajić, M., Ristanović, M., Nikolić, A.,& Krivokapić, Z.. (2018). Polymorphism RAD51 172G > T in Serbian patients with colorectal cancer. in Journal of Buon
Balkan Union of Oncology (B.U.ON.)., 23(4), 936-940.
https://hdl.handle.net/21.15107/rcub_imagine_1115

Petrović-Sunderić J, Dragičević S, Krnjajić M, Ristanović M, Nikolić A, Krivokapić Z. Polymorphism RAD51 172G > T in Serbian patients with colorectal cancer. in Journal of Buon. 2018;23(4):936-940.
https://hdl.handle.net/21.15107/rcub_imagine_1115 .

Petrović-Sunderić, Jelena, Dragičević, Sandra, Krnjajić, Mina, Ristanović, Momcilo, Nikolić, Aleksandra, Krivokapić, Zoran, "Polymorphism RAD51 172G > T in Serbian patients with colorectal cancer" in Journal of Buon, 23, no. 4 (2018):936-940,
https://hdl.handle.net/21.15107/rcub_imagine_1115 .

TY  - JOUR
AU  - Nikolić, Aleksandra
AU  - Vlajnić, Marina
AU  - Ristanović, Momcilo
AU  - Petrović, Jelena
AU  - Dimitrijević, Ivan
AU  - Krivokapić, Zoran
AU  - Radojković, Dragica
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1036
AB  - Purpose: To analyze if cell free (cf)DNA levels and the presence of KRAS and BRAF mutations in serum could be used as diagnostic biomarkers in patients with primary colorectal cancer (CRC). Methods: This study included 92 individuals who were operated due to primary CRC (N=52;study group) and to hemorrhoids (N=40;control group). Serum cfDNA levels were measured with real-time PCR (RT-PCR) using PicoGreen dsDNA quantitation reagent. Colorectal tissue and related blood and serum samples taken at the time of surgery were subjected to DNA extraction and analysis of KRAS and BRAF mutations based on multiplex SNaPshot assay and DNA sequencing. Results: The average cfDNA concentration was lower in patients of the study group (20 +/- 7 ng/mu L) in comparison to controls (34 +/- 9 ng/mu L) and this difference was statistically significant (p lt 0.001). The SNaPshot analysis detected KRAS c35 mutations in colorectal tumor tissue in 14 cases, but the presence of the mutation was not confirmed in cfD-NA extracted from blood samples of these patients. Conclusions: The level of serum cfDNA in CRC is decreased in comparison to patients with hemorrhoids, which questions the usefulness of cfDNA as cancer biomarker. Also, cfDNA does not appear to be suitable as a source for mutation detection in this disease.
PB  - Balkan Union of Oncology (B.U.ON.)
T2  - Journal of Buon
T1  - Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer
EP  - 183
IS  - 1
SP  - 178
VL  - 22
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1036
ER  - 

@article{
author = "Nikolić, Aleksandra and Vlajnić, Marina and Ristanović, Momcilo and Petrović, Jelena and Dimitrijević, Ivan and Krivokapić, Zoran and Radojković, Dragica",
year = "2017",
abstract = "Purpose: To analyze if cell free (cf)DNA levels and the presence of KRAS and BRAF mutations in serum could be used as diagnostic biomarkers in patients with primary colorectal cancer (CRC). Methods: This study included 92 individuals who were operated due to primary CRC (N=52;study group) and to hemorrhoids (N=40;control group). Serum cfDNA levels were measured with real-time PCR (RT-PCR) using PicoGreen dsDNA quantitation reagent. Colorectal tissue and related blood and serum samples taken at the time of surgery were subjected to DNA extraction and analysis of KRAS and BRAF mutations based on multiplex SNaPshot assay and DNA sequencing. Results: The average cfDNA concentration was lower in patients of the study group (20 +/- 7 ng/mu L) in comparison to controls (34 +/- 9 ng/mu L) and this difference was statistically significant (p lt 0.001). The SNaPshot analysis detected KRAS c35 mutations in colorectal tumor tissue in 14 cases, but the presence of the mutation was not confirmed in cfD-NA extracted from blood samples of these patients. Conclusions: The level of serum cfDNA in CRC is decreased in comparison to patients with hemorrhoids, which questions the usefulness of cfDNA as cancer biomarker. Also, cfDNA does not appear to be suitable as a source for mutation detection in this disease.",
publisher = "Balkan Union of Oncology (B.U.ON.)",
journal = "Journal of Buon",
title = "Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer",
pages = "183-178",
number = "1",
volume = "22",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1036"
}

Nikolić, A., Vlajnić, M., Ristanović, M., Petrović, J., Dimitrijević, I., Krivokapić, Z.,& Radojković, D.. (2017). Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer. in Journal of Buon
Balkan Union of Oncology (B.U.ON.)., 22(1), 178-183.
https://hdl.handle.net/21.15107/rcub_imagine_1036

Nikolić A, Vlajnić M, Ristanović M, Petrović J, Dimitrijević I, Krivokapić Z, Radojković D. Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer. in Journal of Buon. 2017;22(1):178-183.
https://hdl.handle.net/21.15107/rcub_imagine_1036 .

Nikolić, Aleksandra, Vlajnić, Marina, Ristanović, Momcilo, Petrović, Jelena, Dimitrijević, Ivan, Krivokapić, Zoran, Radojković, Dragica, "Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer" in Journal of Buon, 22, no. 1 (2017):178-183,
https://hdl.handle.net/21.15107/rcub_imagine_1036 .

TY  - JOUR
AU  - Nikolić, Aleksandra
AU  - Kojić, Snežana
AU  - Knezević, Srbislav
AU  - Krivokapić, Zoran
AU  - Ristanović, Momcilo
AU  - Radojković, Dragica
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/543
AB  - Background: The tumor suppressor gene SMAD4 (DPC4) encodes for the common intracellular mediator of the TGF-beta superfamily pathway, which regulates numerous cellular processes, such as cell proliferation, cell differentiation, apoptosis, cell fate and migration. This study was aimed to investigate the presence of genetic variants in SMAD4 gene promoter in malignant pancreatic and colorectal tissue and to analyze their functional consequences. Methods: The study was performed on genomic DNA isolated from malignant tissue samples obtained on surgery from 50 patients with pancreatic carcinoma and 50 patients with colorectal cancer. Screening for mutations within an 800 bp-long fragment of the SMAD4 gene promoter was performed by DNA sequencing and two mononucleotide repeats, at positions -462 and -4, were found to be polymorphic in malignant tissue. The exact number of thymidines in the tracts -462T(15) and -4T(12) was determined by PCR with fluorescently labeled primers followed by capillary electrophoresis. Functional analysis of -462T(15)/-4T(12) haplotypes was performed by luciferase reporter assays. Results: Haplotype -462T(14)/-4T(10) was found in 85% of pancreatic cancer tissues, but it was not present in any of colorectal cancer tissues. Statistically significant reduction (p  lt  0.001) in activity was observed in the haplotype -462T(14)/-4T(10) in comparison with the haplotypes -462T(15)/-4T(12) and -462T(14)/-4T(11). Conclusion: Results of this study indicate that novel genetic variant -4T(10) in the SMAD4 gene promoter affects its activity and that element -4T(12) may play a role in transcriptional regulation of SMAD4 gene expression. Obtained results, though preliminary, also indicate that SMAD4 gene promoter haplotype -462T(14)/-4T(10) may represent a genetic marker of potential relevance for pancreatic and colorectal cancer. The findings of this study should be confirmed by further investigation in these two and other tumors, on larger number of patients and with different tumor stages. Translational research aimed at investigating potential application of mononucleotide repeats -462T(15) and -4T(12) in SMAD4 gene promoter as molecular markers in cancer may also prove useful.
PB  - Elsevier Sci Ltd, Oxford
T2  - Cancer Epidemiology
T1  - Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: Detection of two novel polymorphic nucleotide repeats
EP  - 271
IS  - 3
SP  - 265
VL  - 35
DO  - 10.1016/j.canep.2010.10.002
ER  - 

@article{
author = "Nikolić, Aleksandra and Kojić, Snežana and Knezević, Srbislav and Krivokapić, Zoran and Ristanović, Momcilo and Radojković, Dragica",
year = "2011",
abstract = "Background: The tumor suppressor gene SMAD4 (DPC4) encodes for the common intracellular mediator of the TGF-beta superfamily pathway, which regulates numerous cellular processes, such as cell proliferation, cell differentiation, apoptosis, cell fate and migration. This study was aimed to investigate the presence of genetic variants in SMAD4 gene promoter in malignant pancreatic and colorectal tissue and to analyze their functional consequences. Methods: The study was performed on genomic DNA isolated from malignant tissue samples obtained on surgery from 50 patients with pancreatic carcinoma and 50 patients with colorectal cancer. Screening for mutations within an 800 bp-long fragment of the SMAD4 gene promoter was performed by DNA sequencing and two mononucleotide repeats, at positions -462 and -4, were found to be polymorphic in malignant tissue. The exact number of thymidines in the tracts -462T(15) and -4T(12) was determined by PCR with fluorescently labeled primers followed by capillary electrophoresis. Functional analysis of -462T(15)/-4T(12) haplotypes was performed by luciferase reporter assays. Results: Haplotype -462T(14)/-4T(10) was found in 85% of pancreatic cancer tissues, but it was not present in any of colorectal cancer tissues. Statistically significant reduction (p  lt  0.001) in activity was observed in the haplotype -462T(14)/-4T(10) in comparison with the haplotypes -462T(15)/-4T(12) and -462T(14)/-4T(11). Conclusion: Results of this study indicate that novel genetic variant -4T(10) in the SMAD4 gene promoter affects its activity and that element -4T(12) may play a role in transcriptional regulation of SMAD4 gene expression. Obtained results, though preliminary, also indicate that SMAD4 gene promoter haplotype -462T(14)/-4T(10) may represent a genetic marker of potential relevance for pancreatic and colorectal cancer. The findings of this study should be confirmed by further investigation in these two and other tumors, on larger number of patients and with different tumor stages. Translational research aimed at investigating potential application of mononucleotide repeats -462T(15) and -4T(12) in SMAD4 gene promoter as molecular markers in cancer may also prove useful.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Cancer Epidemiology",
title = "Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: Detection of two novel polymorphic nucleotide repeats",
pages = "271-265",
number = "3",
volume = "35",
doi = "10.1016/j.canep.2010.10.002"
}

Nikolić, A., Kojić, S., Knezević, S., Krivokapić, Z., Ristanović, M.,& Radojković, D.. (2011). Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: Detection of two novel polymorphic nucleotide repeats. in Cancer Epidemiology
Elsevier Sci Ltd, Oxford., 35(3), 265-271.
https://doi.org/10.1016/j.canep.2010.10.002

Nikolić A, Kojić S, Knezević S, Krivokapić Z, Ristanović M, Radojković D. Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: Detection of two novel polymorphic nucleotide repeats. in Cancer Epidemiology. 2011;35(3):265-271.
doi:10.1016/j.canep.2010.10.002 .

Nikolić, Aleksandra, Kojić, Snežana, Knezević, Srbislav, Krivokapić, Zoran, Ristanović, Momcilo, Radojković, Dragica, "Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: Detection of two novel polymorphic nucleotide repeats" in Cancer Epidemiology, 35, no. 3 (2011):265-271,
https://doi.org/10.1016/j.canep.2010.10.002 . .