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Povzetek: Background: Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, plays a crucial role in focal adhesion turnover by interfacing between the extracellular space, transmembrane integrins, and actin filaments. Its significance for the progression of several malignancies, including bladder cancer, has been well-documented. However, its precise role and the implications of its inhibition in bladder cancer tissues and urothelial in vitro models has not been fully explored. This study examined FAK expression and function in human bladder cancer biopsies and in vitro bladder cancer models. Materials and methods: Ex vivo analyses were performed using reverse transcription-quantitative PCR (qRT-PCR), western blotting, and immunohistochemistry to compare FAK expression between bladder cancer tissues and adjacent normal tissues. In vitro, FAK expression was assessed in low-grade (LG) human non-invasive papilloma urothelial cell line RT4 for NMIBC (Ta), high-grade (HG) human muscle-invasive cancer urothelial cell line T24 for MIBC (T2) and normal porcine urothelial (NPU) cells using qRT-PCR and western blotting, as well as flow cytometry for the quantification of FAK-positive RT4 and T24 cells. The role of FAK in cancer cell survival was explored in vitro using microRNA (miRNA) to silence FAK expression. Additionally, we used FAK inhibitors PND-1186, PF-573228 and defactinib to investigate the effects of FAK inhibition on normal compared to cancerous bladder urothelial cells. Results: Ex vivo analyses demonstrated significantly higher FAK expression in bladder cancer tissues compared to adjacent normal tissues. Similarly, in vitro analyses showed significantly higher FAK expression in RT4 and T24 cells than NPU cells. Silencing FAK using anti-FAK plasmids led to increased caspase-3-mediated apoptosis of RT4 and T24 cells and growth reduction of stably transfected T24 cells. Importantly, based on cell viability assays, treatment with 100 μM defactinib for 2 hours per day on 3 consecutive days was identified as a clinically relevant regimen. Under this treatment, the viability of differentiated NPU cells remained high at 108.4 ± 17.1%, while the viability of 2-day RT4 and 2-day T24 cells was drastically reduced to 4.1 ± 2.7% and 7.6 ± 2.9%, respectively. Conclusions: To our knowledge, this is the first report demonstrating the role of FAK and its inhibition across both normal and cancerous bladder urothelial models. This study highlights the critical role of FAK in the progression of human bladder cancer and establishes a foundation for exploring FAK inhibition as a potential therapeutic approach in bladder cancer treatment.
Ključne besede: bladder cancer, defactinib, focal adhesion kinase, human urothelial carcinoma, urothelial cell
Objavljeno v DiRROS: 09.12.2025; Ogledov: 105; Prenosov: 52
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Povzetek: Electronic patient-reported outcomes (ePROs) are gaining importance. The aim of this study was to investigate the difference in the reporting of symptoms between patients via mobile application (m-app) and doctor assessments. Additionally, usability and satisfaction with the use of the m-app were assessed. Methods: In this single-center prospective cohort study, we analyzed ePROs in 46 patients receiving (neo)adjuvant chemotherapy for early breast cancer. Patients recorded the occurrence and intensity of symptoms via the Android-based m-app daily. Three-monthly, patients completed validated quality of life questionnaires (EORTC C30 and BR23). For the 10 most common symptoms reported by patients, we compared the frequencies and grades between patients and doctors. Additionally, we compared daily symptom reports with questionnaire results. Finally, the usefulness of and level of satisfaction with the m-app by patients and doctors were evaluated. Results: During the study, patients recorded almost twice as many different symptoms through the m-app as doctors did in the electronic health records (75 vs 49). Symptoms were described by patients as mild (67%), moderate (30%), or severe (3%). The frequency and intensity of symptoms reported by patients were significantly higher than those reported by doctors (p<0.001). Fatigue, insomnia and dry mouth were the three main symptoms reported in more than 75% of patients, but insomnia and dry mouth were also the symptoms most often underreported by doctors. After three months of chemotherapy, QoL assessments revealed worsening of physical, social, cognitive and role functioning, increased fatigue, systemic therapy side effects, and dyspnea but a reduction in arm and shoulder problems. Patients and doctors rated the m-app with an overall score of 4.5 out of 5 (IQR 1.0). Patients expressed high levels of satisfaction with and usability of the m-app. In contrast, doctors were somewhat reluctant to perceive ePROs as an additional burden with patient management. Conclusion: This study revealed a significant discrepancy between patients’ daily symptom reports via the m-app and doctors’ assessments, indicating that healthcare professionals may not fully capture patients’ experiences. This underscores the importance of integrating PROs to accurately evaluate patients’ conditions. Our m-app serves as a promising tool for reporting and managing side effects during systemic treatment of breast cancer.
Ključne besede: breast cancer, mobile application, patients, doctors
Objavljeno v DiRROS: 05.12.2025; Ogledov: 106; Prenosov: 42
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Povzetek: This epidemiological study aims to assess the cancer risk potentially associated with environmental exposure resulting from cement production and waste co-incineration at the Anhovo cement plant in Western Slovenia and to develop a strong and reliable methodological framework for the long-term surveillance of environmentally related cancer risks in small geographical areas. Materials and methods We integrated all the available data sources: cancer cases from the population-based Slovenian Cancer Registry; background population; and available measurements on exposure to air PM10 particles and chromium (Cr) in the soil in the municipality of Kanal and the wider Goriška region. Relative risks of cancer in small geographical areas were estimated using Bayesian hierarchical spatial models and the population attributable fractions of the modelled risk factors were calculated. The point source analysis compared the cancer risk near the cement plant to that in more distant areas. Results The analysis did not reveal any excess cancer incidence in the area of the Anhovo cement plant or an association with the PM10 particles and Cr in the soil. The incidence of mesothelioma remains high in the region, but stable in the last two decades. Conclusions In view of the environmental pollution caused by either historical cement production or the potential impact of current waste co-incineration activities in Kanal, we strongly recommend that a follow-up epidemiological study be carried out in the next 10 to 20 years. The methodological framework established in the present study provides a foundation for the ongoing surveillance of the cancer burden in the region.
Ključne besede: cancer incidence, environmental exposure, cancer data
Objavljeno v DiRROS: 05.12.2025; Ogledov: 81; Prenosov: 0

Povzetek: Bisphenol A (BPA) is a high-production-volume industrial chemical and component of commonly used plastic products. However, it is also an endocrine-disrupting chemical that can negatively affect human health. It is not yet known whether it is associated with the development of epithelial ovarian cancer (EOC), a severe and highly fatal human disease. Therefore, the purpose of this study was to determine the concentrations of BPA in the urine of women with EOC or epithelial borderline ovarian tumors (EBOTs) using gas chromatography tandem mass spectrometry (GC-MS/MS) and find their possible associations with kidney function at the molecular level, urine and blood biochemical parameters related to metabolism, anti-Müllerian hormone (AMH) (a marker of ovarian reserve/fertility), and lifestyle habits determined via a questionnaire in comparison to healthy controls. The results suggest that the unadjusted or urine-specific-gravity-adjusted BPA levels were significantly increased in women with EOC/EBOT. The unadjusted BPA was significantly positively associated with urinary creatinine (p = 0.007) in all women with EOC/EBOT after adjustment for age, body mass index, and pregnancy using multiple linear regression analysis. This may be related to kidney injury. However, no association was found between urinary BPA and serum AMH levels in women. Women with ovarian malignancies were more exposed to plastic products for storing foods and drinks. Some lifestyle habits, including refilling plastic bottles, correlate with higher urinary BPA levels across the entire cohort of women. When considering EOC or EBOT, it is necessary to consider the potential higher exposure of women to BPA, as reflected in their urine and lifestyle habits.
Ključne besede: anti-Müllerian hormone, kidney function, lifestyle habits, ovarian cancer, thrombocytes, urine, female exposure
Objavljeno v DiRROS: 03.12.2025; Ogledov: 177; Prenosov: 77
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Povzetek: Pancreatic cancer is among the deadliest malignancies, with limited treatment options and poor prognosis. Novel strategies are therefore urgently needed. Sotorasib, a KRAS G12C-specific inhibitor, offers targeted treatment for a small subset of patients with this mutation. Electrochemotherapy (ECT), which enhances the cytotoxicity of chemotherapeutic agents through electroporation-induced membrane permeabilization, has shown promise in various tumor types, including deep-seated malignancies such as pancreatic cancer. Combining ECT with sotorasib may potentiate antitumor effects in KRAS G12C-mutated pancreatic cancer; however, preclinical data on such combinations are lacking. This proof-of-concept study evaluated the cytotoxic effects of ECT using bleomycin (BLM) or cisplatin (CDDP) in combination with sotorasib in KRAS G12C-mutated MIA PaCa-2 and KRAS G12D-mutated PANC-1 pancreatic cancer cell lines. ECT alone significantly reduced cell viability, particularly in MIA PaCa-2 cells, where electric pulses induced approximately 75% cell death. Combining ECT with sotorasib resulted in an additive effect on KRAS G12C-mutated MIA PaCa-2 cells, though no synergy was observed, likely due to the high intrinsic sensitivity to electric pulses. These results support the potential of combining physical and molecular therapies in a subset of pancreatic cancer patients and lay the groundwork for further in vivo studies to optimize treatment parameters and explore clinical translatability.
Ključne besede: bleomycin, cisplatin, electrochemotherapy, pancreatic cancer
Objavljeno v DiRROS: 26.11.2025; Ogledov: 113; Prenosov: 51
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