Zora Lasabova | Jessenius faculty of Medicine (original) (raw)
Papers by Zora Lasabova
Frontiers in Oncology
IntroductionColorectal cancer (CRC) is a heterogeneous disease caused by molecular changes, as dr... more IntroductionColorectal cancer (CRC) is a heterogeneous disease caused by molecular changes, as driver mutations, gene methylations, etc., and influenced by tumor microenvironment (TME) pervaded with immune cells with both pro- and anti-tumor effects. The studying of interactions between the immune system (IS) and the TME is important for developing effective immunotherapeutic strategies for CRC. In our study, we focused on the analysis of expression profiles of inflammatory and immune-relevant genes to identify aberrant signaling pathways included in carcinogenesis, metastatic potential of tumors, and association of Kirsten rat sarcoma virus (KRAS) gene mutation.MethodsA total of 91 patients were enrolled in the study. Using NGS, differential gene expression analysis of 11 tumor samples and 11 matching non-tumor controls was carried out by applying a targeted RNA panel for inflammation and immunity genes containing 475 target genes. The obtained data were evaluated by the CLC Genomi...
Prenatal Diagnosis, Jul 19, 2018
PubMed, Jun 1, 2012
Objective: To determine the presence of HPV infection and expression level of p16INK4A mRNA trans... more Objective: To determine the presence of HPV infection and expression level of p16INK4A mRNA transcripts in cervical smears as adjunct biomarker in detection of cervical intraepithelial neoplasia or cancer. Design: Prospective pilot clinical study assessing clinical utility and validity of ddCt method for qPCR mRNA expression of p16ink4a in comparison to immunohistochemistry. Setting: Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. Methods: Cervical smears (OC) from patients with different cervical lesions (L-SIL, H-SIL, SCA; n=45) and from healthy controls (n=45) were tested for the presence of HPV infection and p16INK4A mRNA transcripts using relative quantification (RQ). Results were compared to H&E and IHC histological findings from biopsies (conization, hysterectomy). Results: HPV 16 was the most frequent finding (53.3%) in the group of subjects with cervical dysplasia. The p16INK4A mRNA expression analysis revealed the slightly reduced expression in L-SIL group, 4-fold increased expression in H-SIL and 10-fold increase in women with SCA when compared to controls. The p16INK4A mRNA expression in OC was present in 30% of L-SIL, 75% of H-SIL and 85.7% of SCA samples, respectively. The test overall sensitivity was 81.48% (95% CI: 61.92-93.7) and specificity 60% (95% CI: 26.24- 87.84) with PPV of 84.62% and NPV of 54.55%. The likelihood ratio (LR) in case of test positivity was 2.04 and for negativity 0.31. The diagnostic accuracy of p16INK4A expression by RQ method in OC smears for prediction of p16 positivity in cervical dysplasia was 66.7% for the L-SIL lesions, 59.5% for H-SIL lesions, and 100% for SCA (r=0.9897, p<0.0913) when compared to IHC p16 positive findings in surgically treated samples. Conclusion: The relative quantification is able to determine the level of p16INK4A mRNA transcripts in cervical smear cells with active carcinogenesis nearly at the same level as IHC staining. The advance of biopsy sparing over IHC is qualifying this diagnostic approach for useful candidate in selective management of women with cervical dysplasia looking for cervix preservation or avoiding the unnecessary overtreatment.
Journal of Clinical Oncology, May 20, 2017
e17060 Background: BRCA1/2 mutations represent first genetically defined predictive markers for t... more e17060 Background: BRCA1/2 mutations represent first genetically defined predictive markers for targeted therapy of patients with recurrent high-grade serous carcinoma (HGSC), therefore patients with HGSC should be tested for a germline and somatic BRCA mutation (g BRCAm and s BRCAm, resp.). In our study we analyzed possibilities and limits for determination of both origin and pathogenicity of mutations detected by HGSC biopsies analyses. Methods: We present data obtained by massive parallel sequencing on Miseq (Illumina). Library for sequencing was prepared by Somatic BRCA Tumor MASTR Plus kit (Multiplicom) from DNA isolated from HGSC FFPE tissue of 42 patients allowing simultaneous identification of g BRCAm and s BRCAm. For the pathogenicity evaluations we followed American College of Medical Genetics and Genomics (ACMG) criteria and used various bioinformatic tools. Results: All sequencing data were interpreted by SOPHIA DDM (Sophia Genetics) commercial tool. BRCA1/2 mutation was absent in 43% and present in 50% of patients, while 7% of cases had to be retested due to low coverage. Data of 28/42 patients were analyzed also by Ingenuity (Qiagen), the comparison of both the tools identified discrepant pathogenic determinationin 29% of them. The discrepancies in origin and pathogenicity of already detected mutations were found also by analyzing the data in other non-commercial databases (dbSNP, COSMIC, ClinVar, BIC, etc.). Conclusions: At least in a certain proportion of the cases, the data obtained by HGSC biopsy specimen mutational analyses and interpreted by accessible bioinformatic tools may lead to an equivocal assessment of both origin and pathogenicity of detected BRCA1/2 mutations. Other studies are necessary to eliminate the observed discrepancies.
European Journal of Cancer, Jul 1, 2016
Physiological Research, Dec 31, 2021
PubMed, Aug 1, 2014
Objective: To determine the presence of mutations in exon 9 (encoding the helical domain) and exo... more Objective: To determine the presence of mutations in exon 9 (encoding the helical domain) and exon 20 (encoding the kinase domain) of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene in DNA obtained from paraffin embedded tissue from patients with carcinoma of the mammary gland and to correlate results with clinicopathological characteristics of cancer. Design: Prospective clinical study. Setting: Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Commenius University, Martin, Slovak Republic. Methods: In set of 95 tissue samples from patients with breast cancer, mutations in exon 9 and 20 were analysed by sequencing. We also observed the associations between mutations and histopathological characteristics of tumor. Results: Overall, mutations were present in 25.3% (24/95) of PIK3CA gene, of this 14.7% (14/95) of mutations were located in exon 9 and 10.5% (10/95) of mutations were in exon 20. We detected three "hotspot" mutations, two were located in exon 9 (E542K, E545K) and the third mutation was found in exon 20 (H1047R). Mutations in exon 9 showed significant correlation with lower grade(p = 0.0074) and pN status without metastases(p = 0.0415). Mutations in exon 20 were associated with higher age of patient (p = 0.0249). The E545K mutation correlated with lower grade (p = 0.0013) and pN status (p = 0.0232) particularly; the H1047R mutation was significantly more frequent in lobular type of breast cancer (p = 0.0354). Conclusion: The PI3K signaling pathway plays a critical oncogenic role in the development of human breast cancer and the prevalence of its deregulation advocates its potential as a feasible therapeutic target. In our study we demonstrate a significant correlation between the presence of PIK3CA mutations and some clinicopathological characteristics of tumour. We have shown that the mutations in exon 9 of PIK3CA were associated with favourable prognostic factors. Keywords: "hotspot" mutation, PIK3CA, PI3K pathway, breast cancer.
Prenatal Diagnosis, Dec 1, 2017
Frontiers in Pediatrics, May 25, 2022
Neoplasma, 2020
There is a great effort to connect the accumulation of 2-hydroxyglutarate (2-HG) oncometabolite w... more There is a great effort to connect the accumulation of 2-hydroxyglutarate (2-HG) oncometabolite with cellular onco-epigenetic status and subsequently predict the prognoses of glioma patients. In this observational study, the concentrations of D- and L- 2-HG were determined in 57 tumor tissue samples of glioma patients (n = 57) WHO grade I through IV (astrocytoma, oligodendroglioma, secondary glioblastoma and glioblastoma multiforme) in vitro. Also, genetic mutation status on isocitrate dehydrogenase 1 and 2 (IDH 1/2) was determined from these samples. The objective of this study was to confirm or to reject the hypothesis of the direct correlation of 2-HG concentration in tumor tissue and the results from IDH 1/IDH 2 point mutation analyses. The concentrations of 2-HG were quantified using high sensitive HPLC and Q-TOF HRMS spectrometer setup. Concurrently, the genetic mutation analyses of both IDH 1 (cytosolic) and IDH 2 (mitochondrial) were performed by the isolation of tumor tissu...
Pathology - Research and Practice, 2020
BRAF V600E mutations in GISTs are considered to be one of the mutational events in KIT/PDGFRA neg... more BRAF V600E mutations in GISTs are considered to be one of the mutational events in KIT/PDGFRA negative or positive GISTs, respectively. BRAF mutated GISTs usually do not respond to imatinib treatment, even more GISTs with imatinib sensitive KIT mutation. However, they are almost phenotypically and morphologically identical with KIT/PDGFRA positive GISTs. In general, due to the small number of BRAF mutations in GIST and because of the rarity of concomitant BRAF/KIT or BRAF/PDGFRA mutations, their frequency may be depreciated. The aim of this study was BRAF mutation detection in KIT/PDGFRA positive GISTs and their verification by other molecular methods. We applied the sensitive droplet digital PCR on 35 randomly selected KIT/PDGFRA positive GISTs to detect V600E mutations. We have established two criteria for the evaluation of samples: false positive rate (FPR) based on the negative controls; Limit of Detection (LoD) based on the serial dilution of positive control from RKO cell line harboring heterozygous V600E mutation in constant wild-type DNA background. Results from ddPCR were verified by other molecular methods: allele-specific PCR, dideoxysequencing, competitive allele-specific TaqMan PCR (castPCR). FPR was determined as 5 (∼4.4) positive droplets, and LoD was assessed to 3.4293 copies/μL what is the method sensitivity of 0.0162 %. We identified eight KIT/PDGFRA positive patients with concomitant V600E mutation. The five of them were in coexistence with KIT mutation and three with PDGFRA mutation. We also included the liver metastasis, but data from primary tumour were not available. We achieved the very high sensitivity of the ddPCR method for detecting BRAF mutation in GISTs to have importance from the point of view of therapy.
Seminars in Thrombosis and Hemostasis, 2019
Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the ... more Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD). Molecular testing in VWD patients has shown high variability in the overall genetic background of this condition. Almost 600 mutations and many disease-causing mechanisms have been described in the 35 years since the VWF gene was identified. Genetic testing in VWD patients is now available in many centers as a part of the VWD diagnostic algorithm. Molecular mechanisms leading to types 2 and 3 VWD are well characterized; thus, information from genetic analysis in these VWD types may be beneficial for their correct classification. However, the molecular basis of type 1 VWD is still not fully elucidated and most likely represents a multifactorial disorder reflecting a combined impact of environmental and genetic factors within and outside of VWF. Regarding sequencing methods, the previous gold-s...
Genetic Testing and Molecular Biomarkers, 2018
AIMS The aim of our study was to investigate possible associations between three SNPs: rs4673 in ... more AIMS The aim of our study was to investigate possible associations between three SNPs: rs4673 in the CYBA gene; rs1041740 in the SOD1 gene; and rs1001179 in the CAT gene, and type 1 diabetes (T1D) or diabetic peripheral neuropathy (DPN) in T1D patients. MATERIALS AND METHODS Allelic variants of the selected SNPs were determined by allelic discrimination assays in 114 T1D patients enrolled in the study group and in 90 healthy individuals from a control group. Associations between each of the three SNPs were tested in subgroups of T1D patients divided according to the presence of DPN. RESULTS The TT genotype of rs4673 in the CYBA gene was associated with DPN in T1D patients (OR 4.997, 95% CI 1.403-19.083, p = 0.016). Weak significance was observed for a protective effect of the TT genotype of rs1041740 in the SOD1 gene relative to T1D development (OR 0.318, 95% CI 0.092-0.959, p = 0.056). There was no significant association between the CAT gene SNP rs1001179 and T1D or DPN. CONCLUSION We showed a strong association of the CYBA polymorphism rs4673 with DPN in Slovak children and adolescents with T1D. Further studies are necessary to assess the relationship between rs1041740 and T1D or DPN.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2017
Breast cancer is the most common malignancy in women worldwide. Over 90% of all breast cancer cas... more Breast cancer is the most common malignancy in women worldwide. Over 90% of all breast cancer cases are of different 'sporadic' cell types, thus placing emphasis on the need for breast cancer prevention and new effective treatment strategies. In recent years, pre-clinical research provides growing evidence regarding the beneficial action of bioactive plant-derived substances - phytochemicals, on multiple cancer-related biological pathways. The important natural source of various phytochemicals with anti-oncogenic properties are plant-based functional foods. It is hypothesized that a significant anti-tumour activity of plant-based functional foods are the result of a combination of various phytochemicals rather than an isolated agent. The mixture of phytochemicals with various biological activities present in whole foods could have additive or synergistic effects against carcinogenesis. Clinically, it is very important to compare the effect of the isolated phytochemicals agai...
Frontiers in Oncology
IntroductionColorectal cancer (CRC) is a heterogeneous disease caused by molecular changes, as dr... more IntroductionColorectal cancer (CRC) is a heterogeneous disease caused by molecular changes, as driver mutations, gene methylations, etc., and influenced by tumor microenvironment (TME) pervaded with immune cells with both pro- and anti-tumor effects. The studying of interactions between the immune system (IS) and the TME is important for developing effective immunotherapeutic strategies for CRC. In our study, we focused on the analysis of expression profiles of inflammatory and immune-relevant genes to identify aberrant signaling pathways included in carcinogenesis, metastatic potential of tumors, and association of Kirsten rat sarcoma virus (KRAS) gene mutation.MethodsA total of 91 patients were enrolled in the study. Using NGS, differential gene expression analysis of 11 tumor samples and 11 matching non-tumor controls was carried out by applying a targeted RNA panel for inflammation and immunity genes containing 475 target genes. The obtained data were evaluated by the CLC Genomi...
Prenatal Diagnosis, Jul 19, 2018
PubMed, Jun 1, 2012
Objective: To determine the presence of HPV infection and expression level of p16INK4A mRNA trans... more Objective: To determine the presence of HPV infection and expression level of p16INK4A mRNA transcripts in cervical smears as adjunct biomarker in detection of cervical intraepithelial neoplasia or cancer. Design: Prospective pilot clinical study assessing clinical utility and validity of ddCt method for qPCR mRNA expression of p16ink4a in comparison to immunohistochemistry. Setting: Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. Methods: Cervical smears (OC) from patients with different cervical lesions (L-SIL, H-SIL, SCA; n=45) and from healthy controls (n=45) were tested for the presence of HPV infection and p16INK4A mRNA transcripts using relative quantification (RQ). Results were compared to H&E and IHC histological findings from biopsies (conization, hysterectomy). Results: HPV 16 was the most frequent finding (53.3%) in the group of subjects with cervical dysplasia. The p16INK4A mRNA expression analysis revealed the slightly reduced expression in L-SIL group, 4-fold increased expression in H-SIL and 10-fold increase in women with SCA when compared to controls. The p16INK4A mRNA expression in OC was present in 30% of L-SIL, 75% of H-SIL and 85.7% of SCA samples, respectively. The test overall sensitivity was 81.48% (95% CI: 61.92-93.7) and specificity 60% (95% CI: 26.24- 87.84) with PPV of 84.62% and NPV of 54.55%. The likelihood ratio (LR) in case of test positivity was 2.04 and for negativity 0.31. The diagnostic accuracy of p16INK4A expression by RQ method in OC smears for prediction of p16 positivity in cervical dysplasia was 66.7% for the L-SIL lesions, 59.5% for H-SIL lesions, and 100% for SCA (r=0.9897, p<0.0913) when compared to IHC p16 positive findings in surgically treated samples. Conclusion: The relative quantification is able to determine the level of p16INK4A mRNA transcripts in cervical smear cells with active carcinogenesis nearly at the same level as IHC staining. The advance of biopsy sparing over IHC is qualifying this diagnostic approach for useful candidate in selective management of women with cervical dysplasia looking for cervix preservation or avoiding the unnecessary overtreatment.
Journal of Clinical Oncology, May 20, 2017
e17060 Background: BRCA1/2 mutations represent first genetically defined predictive markers for t... more e17060 Background: BRCA1/2 mutations represent first genetically defined predictive markers for targeted therapy of patients with recurrent high-grade serous carcinoma (HGSC), therefore patients with HGSC should be tested for a germline and somatic BRCA mutation (g BRCAm and s BRCAm, resp.). In our study we analyzed possibilities and limits for determination of both origin and pathogenicity of mutations detected by HGSC biopsies analyses. Methods: We present data obtained by massive parallel sequencing on Miseq (Illumina). Library for sequencing was prepared by Somatic BRCA Tumor MASTR Plus kit (Multiplicom) from DNA isolated from HGSC FFPE tissue of 42 patients allowing simultaneous identification of g BRCAm and s BRCAm. For the pathogenicity evaluations we followed American College of Medical Genetics and Genomics (ACMG) criteria and used various bioinformatic tools. Results: All sequencing data were interpreted by SOPHIA DDM (Sophia Genetics) commercial tool. BRCA1/2 mutation was absent in 43% and present in 50% of patients, while 7% of cases had to be retested due to low coverage. Data of 28/42 patients were analyzed also by Ingenuity (Qiagen), the comparison of both the tools identified discrepant pathogenic determinationin 29% of them. The discrepancies in origin and pathogenicity of already detected mutations were found also by analyzing the data in other non-commercial databases (dbSNP, COSMIC, ClinVar, BIC, etc.). Conclusions: At least in a certain proportion of the cases, the data obtained by HGSC biopsy specimen mutational analyses and interpreted by accessible bioinformatic tools may lead to an equivocal assessment of both origin and pathogenicity of detected BRCA1/2 mutations. Other studies are necessary to eliminate the observed discrepancies.
European Journal of Cancer, Jul 1, 2016
Physiological Research, Dec 31, 2021
PubMed, Aug 1, 2014
Objective: To determine the presence of mutations in exon 9 (encoding the helical domain) and exo... more Objective: To determine the presence of mutations in exon 9 (encoding the helical domain) and exon 20 (encoding the kinase domain) of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene in DNA obtained from paraffin embedded tissue from patients with carcinoma of the mammary gland and to correlate results with clinicopathological characteristics of cancer. Design: Prospective clinical study. Setting: Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Commenius University, Martin, Slovak Republic. Methods: In set of 95 tissue samples from patients with breast cancer, mutations in exon 9 and 20 were analysed by sequencing. We also observed the associations between mutations and histopathological characteristics of tumor. Results: Overall, mutations were present in 25.3% (24/95) of PIK3CA gene, of this 14.7% (14/95) of mutations were located in exon 9 and 10.5% (10/95) of mutations were in exon 20. We detected three "hotspot" mutations, two were located in exon 9 (E542K, E545K) and the third mutation was found in exon 20 (H1047R). Mutations in exon 9 showed significant correlation with lower grade(p = 0.0074) and pN status without metastases(p = 0.0415). Mutations in exon 20 were associated with higher age of patient (p = 0.0249). The E545K mutation correlated with lower grade (p = 0.0013) and pN status (p = 0.0232) particularly; the H1047R mutation was significantly more frequent in lobular type of breast cancer (p = 0.0354). Conclusion: The PI3K signaling pathway plays a critical oncogenic role in the development of human breast cancer and the prevalence of its deregulation advocates its potential as a feasible therapeutic target. In our study we demonstrate a significant correlation between the presence of PIK3CA mutations and some clinicopathological characteristics of tumour. We have shown that the mutations in exon 9 of PIK3CA were associated with favourable prognostic factors. Keywords: "hotspot" mutation, PIK3CA, PI3K pathway, breast cancer.
Prenatal Diagnosis, Dec 1, 2017
Frontiers in Pediatrics, May 25, 2022
Neoplasma, 2020
There is a great effort to connect the accumulation of 2-hydroxyglutarate (2-HG) oncometabolite w... more There is a great effort to connect the accumulation of 2-hydroxyglutarate (2-HG) oncometabolite with cellular onco-epigenetic status and subsequently predict the prognoses of glioma patients. In this observational study, the concentrations of D- and L- 2-HG were determined in 57 tumor tissue samples of glioma patients (n = 57) WHO grade I through IV (astrocytoma, oligodendroglioma, secondary glioblastoma and glioblastoma multiforme) in vitro. Also, genetic mutation status on isocitrate dehydrogenase 1 and 2 (IDH 1/2) was determined from these samples. The objective of this study was to confirm or to reject the hypothesis of the direct correlation of 2-HG concentration in tumor tissue and the results from IDH 1/IDH 2 point mutation analyses. The concentrations of 2-HG were quantified using high sensitive HPLC and Q-TOF HRMS spectrometer setup. Concurrently, the genetic mutation analyses of both IDH 1 (cytosolic) and IDH 2 (mitochondrial) were performed by the isolation of tumor tissu...
Pathology - Research and Practice, 2020
BRAF V600E mutations in GISTs are considered to be one of the mutational events in KIT/PDGFRA neg... more BRAF V600E mutations in GISTs are considered to be one of the mutational events in KIT/PDGFRA negative or positive GISTs, respectively. BRAF mutated GISTs usually do not respond to imatinib treatment, even more GISTs with imatinib sensitive KIT mutation. However, they are almost phenotypically and morphologically identical with KIT/PDGFRA positive GISTs. In general, due to the small number of BRAF mutations in GIST and because of the rarity of concomitant BRAF/KIT or BRAF/PDGFRA mutations, their frequency may be depreciated. The aim of this study was BRAF mutation detection in KIT/PDGFRA positive GISTs and their verification by other molecular methods. We applied the sensitive droplet digital PCR on 35 randomly selected KIT/PDGFRA positive GISTs to detect V600E mutations. We have established two criteria for the evaluation of samples: false positive rate (FPR) based on the negative controls; Limit of Detection (LoD) based on the serial dilution of positive control from RKO cell line harboring heterozygous V600E mutation in constant wild-type DNA background. Results from ddPCR were verified by other molecular methods: allele-specific PCR, dideoxysequencing, competitive allele-specific TaqMan PCR (castPCR). FPR was determined as 5 (∼4.4) positive droplets, and LoD was assessed to 3.4293 copies/μL what is the method sensitivity of 0.0162 %. We identified eight KIT/PDGFRA positive patients with concomitant V600E mutation. The five of them were in coexistence with KIT mutation and three with PDGFRA mutation. We also included the liver metastasis, but data from primary tumour were not available. We achieved the very high sensitivity of the ddPCR method for detecting BRAF mutation in GISTs to have importance from the point of view of therapy.
Seminars in Thrombosis and Hemostasis, 2019
Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the ... more Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD). Molecular testing in VWD patients has shown high variability in the overall genetic background of this condition. Almost 600 mutations and many disease-causing mechanisms have been described in the 35 years since the VWF gene was identified. Genetic testing in VWD patients is now available in many centers as a part of the VWD diagnostic algorithm. Molecular mechanisms leading to types 2 and 3 VWD are well characterized; thus, information from genetic analysis in these VWD types may be beneficial for their correct classification. However, the molecular basis of type 1 VWD is still not fully elucidated and most likely represents a multifactorial disorder reflecting a combined impact of environmental and genetic factors within and outside of VWF. Regarding sequencing methods, the previous gold-s...
Genetic Testing and Molecular Biomarkers, 2018
AIMS The aim of our study was to investigate possible associations between three SNPs: rs4673 in ... more AIMS The aim of our study was to investigate possible associations between three SNPs: rs4673 in the CYBA gene; rs1041740 in the SOD1 gene; and rs1001179 in the CAT gene, and type 1 diabetes (T1D) or diabetic peripheral neuropathy (DPN) in T1D patients. MATERIALS AND METHODS Allelic variants of the selected SNPs were determined by allelic discrimination assays in 114 T1D patients enrolled in the study group and in 90 healthy individuals from a control group. Associations between each of the three SNPs were tested in subgroups of T1D patients divided according to the presence of DPN. RESULTS The TT genotype of rs4673 in the CYBA gene was associated with DPN in T1D patients (OR 4.997, 95% CI 1.403-19.083, p = 0.016). Weak significance was observed for a protective effect of the TT genotype of rs1041740 in the SOD1 gene relative to T1D development (OR 0.318, 95% CI 0.092-0.959, p = 0.056). There was no significant association between the CAT gene SNP rs1001179 and T1D or DPN. CONCLUSION We showed a strong association of the CYBA polymorphism rs4673 with DPN in Slovak children and adolescents with T1D. Further studies are necessary to assess the relationship between rs1041740 and T1D or DPN.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2017
Breast cancer is the most common malignancy in women worldwide. Over 90% of all breast cancer cas... more Breast cancer is the most common malignancy in women worldwide. Over 90% of all breast cancer cases are of different 'sporadic' cell types, thus placing emphasis on the need for breast cancer prevention and new effective treatment strategies. In recent years, pre-clinical research provides growing evidence regarding the beneficial action of bioactive plant-derived substances - phytochemicals, on multiple cancer-related biological pathways. The important natural source of various phytochemicals with anti-oncogenic properties are plant-based functional foods. It is hypothesized that a significant anti-tumour activity of plant-based functional foods are the result of a combination of various phytochemicals rather than an isolated agent. The mixture of phytochemicals with various biological activities present in whole foods could have additive or synergistic effects against carcinogenesis. Clinically, it is very important to compare the effect of the isolated phytochemicals agai...