1. Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseasesKatja Goričar, Viljem Kovač, Metoda Dodič-Fikfak, Vita Dolžan, Alenka Franko, 2020, izvirni znanstveni članek Povzetek: Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.
Ključne besede: asbestos-related disease, malignant mesothelioma, mesothelin
Objavljeno v DiRROS: 16.07.2024; Ogledov: 13; Prenosov: 4
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2. The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesotheliomaPetra Piber, Neža Vavpetič, Katja Goričar, Vita Dolžan, Viljem Kovač, Alenka Franko, 2020, izvirni znanstveni članek Povzetek: Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1%). The expression of IL-1% may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods. In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results. We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13%0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14%0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28%0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions. Our findings suggest that genetic variability of inflammatory mediator IL-1% could contribute to the risk of developing MM, but not pleural plaques.
Ključne besede: asbestos, genetic variation, malignant mesothelioma, pleural plaques
Objavljeno v DiRROS: 16.07.2024; Ogledov: 10; Prenosov: 4
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4. Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatmentBarbara Šenk, Katja Goričar, Viljem Kovač, Vita Dolžan, Alenka Franko, 2019, izvirni znanstveni članek Ključne besede: malignant mesothelioma, genetic polymorphism, cisplatin, biomarkers
Objavljeno v DiRROS: 05.07.2024; Ogledov: 67; Prenosov: 19
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6. The influence of genetic variability on the risk of developing malignant mesotheliomaAlenka Franko, Nika Kotnik, Katja Goričar, Viljem Kovač, Metoda Dodič-Fikfak, Vita Dolžan, 2018, izvirni znanstveni članek Ključne besede: malignant mesothelioma, genetic polymorphism, antioxidative enzymes, genetic variability
Objavljeno v DiRROS: 10.06.2024; Ogledov: 111; Prenosov: 39
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9. Long-term survival in glioblastoma : methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factorUroš Smrdel, Mara Popović, Matjaž Zwitter, Emanuela Boštjančič, Andrej Zupan, Viljem Kovač, Damjan Glavač, Drago Bokal, Janja Jerebic, 2016, izvirni znanstveni članek Povzetek: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization). Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p= 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups. Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.
Ključne besede: glioblastoma, long-term survival, methyl guanine methyl transferase, MGMT, prognostic factor
Objavljeno v DiRROS: 30.04.2024; Ogledov: 201; Prenosov: 192
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10. Endobronchial ultrasound elastography strain ratio for mediastinal lymph node diagnosisAleš Rozman, Mateja Marc-Malovrh, Katja Adamič, Tjaša Šubic, Viljem Kovač, Matjaž Fležar, 2015, izvirni znanstveni članek Ključne besede: cancer staging, elastography, endobronchial ultrasound, lung cancer, needle biopsy
Objavljeno v DiRROS: 23.04.2024; Ogledov: 240; Prenosov: 109
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