Browsing by Author "Dragicevic, Sandra (57189326579)"

Background: Altered sphingolipid levels might contribute to rectal cancer development, progression and therapy response by regulating various biological processes, including apoptosis. This study aimed to analyse the serum sphingolipid profile in rectal cancer patients and investigate its association with the apoptotic status of tumour tissue and therapy response. Methods: Ceramide (CER) and sphingomyelin (SM) serum levels were analysed in 22 patients with locally advanced rectal cancer and 24 healthy individuals by ultrafast liquid chromatography coupled with tandem mass spectrometry. The expression of pro-apoptotic BAX (BCL2 associated X, apoptosis regulator) and anti-apoptotic BCL2 (BCL2 apoptosis regulator) was analysed in tumour and corresponding healthy tissue samples of patients by quantitative real-time PCR. Results: Significantly lower serum levels of C18 CER, C22 CER, C24 CER, C18 SM and C24 SM were observed in patients than in controls (P<0.05). For C20 CER, C22 CER and C24 CER, a positive correlation with the pro-apoptotic status of tumour tissue was found (r=0.619, P=0.018; r=0.694, P=0.006 and r=0.601, P=0.023, respectively). No difference in serum sphingolipid levels was found between patients with good, moderate, and poor responses to therapy. Conclusions: These results support the involvement of sphingolipids in rectal cancer. However, further studies, including a larger cohort of subjects, are needed to clarify the association of sphingolipid metabolites with therapy response. © 2025 Society of Medical Biochemists of Serbia. All rights reserved.

Introduction: A recent pan-cancer transcriptome analysis indicated differential activity of alternative promoters of genes TNS3 and LRRFIP1 in head and neck squamous cell carcinoma compared to non-cancerous tissue. The promoters upregulated in head and neck squamous cell carcinoma regulate expression of transcripts TNS3-203 and LRRFIP1-211. Objective: Our aim was to investigate the biomarker potential of TNS3-203 and LRRFIP1-211 transcripts in oral cancer, the most common type of head and neck cancer. Materials and Methods: An in silico approach was used to characterize the promoters and transcripts of interest. Relative expression of TNS3-203 and LRRFIP1-211 transcripts was evaluated by qRT-PCR in a group of 46 oral cancer patients in samples of cancer and adjacent non-cancerous tissue. Results: TNS3-203 was significantly overexpressed in oral cancer compared with matched non-cancerous tissue, so this transcript can potentially be used as a diagnostic biomarker. There were no differences in LRRFIP1-211 level between analyzed tissues. None of the investigated transcripts has prognostic potential in oral cancer. Conclusion: The results obtained indicate the diagnostic potential of TNS3-203, but not LRRFIP1-211 transcript and its role in oral carcinogenesis. © 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Introduction: A recent pan-cancer transcriptome analysis indicated differential activity of alternative promoters of genes TNS3 and LRRFIP1 in head and neck squamous cell carcinoma compared to non-cancerous tissue. The promoters upregulated in head and neck squamous cell carcinoma regulate expression of transcripts TNS3-203 and LRRFIP1-211. Objective: Our aim was to investigate the biomarker potential of TNS3-203 and LRRFIP1-211 transcripts in oral cancer, the most common type of head and neck cancer. Materials and Methods: An in silico approach was used to characterize the promoters and transcripts of interest. Relative expression of TNS3-203 and LRRFIP1-211 transcripts was evaluated by qRT-PCR in a group of 46 oral cancer patients in samples of cancer and adjacent non-cancerous tissue. Results: TNS3-203 was significantly overexpressed in oral cancer compared with matched non-cancerous tissue, so this transcript can potentially be used as a diagnostic biomarker. There were no differences in LRRFIP1-211 level between analyzed tissues. None of the investigated transcripts has prognostic potential in oral cancer. Conclusion: The results obtained indicate the diagnostic potential of TNS3-203, but not LRRFIP1-211 transcript and its role in oral carcinogenesis. © 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Purpose: The RAD51 gene plays an important role in homologous strand exchange in DNA repair. Two common single nucleotide polymorphisms in this gene, 135G>C and 172G>T, were associated with altered gene transcription. While 135G>C was already linked to breast and colorectal cancers in certain populations, 172G>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>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>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>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. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: The RAD51 gene plays an important role in homologous strand exchange in DNA repair. Two common single nucleotide polymorphisms in this gene, 135G>C and 172G>T, were associated with altered gene transcription. While 135G>C was already linked to breast and colorectal cancers in certain populations, 172G>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>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>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>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. © 2018 Zerbinis Publications. All Rights Reserved.

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. © 2022, The Author(s).

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. © 2022, The Author(s).

Inhibitory SMAD7 and common mediator SMAD4 play crucial roles in SMAD-dependent TGF-β 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. © 2021 Elsevier Inc.

Inhibitory SMAD7 and common mediator SMAD4 play crucial roles in SMAD-dependent TGF-β 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. © 2021 Elsevier Inc.