1. Combined toxic effects of BPA and its two analogues BPAP and BPC in a 3D HepG2 cell modelMartina Štampar, Tim Ravnjak, Ana-Marija Domijan, Bojana Žegura, 2023, original scientific article Abstract: Bisphenol A (BPA) is one of the most commonly used substances in the manufacture ofvarious everyday products. Growing concerns about its hazardous properties, including endocrinedisruption and genotoxicity, have led to its gradual replacement by presumably safer analogues inmanufacturing plastics. The widespread use of BPA and, more recently, its analogues has increasedtheir residues in the environment. However, our knowledge of their toxicological profiles is limitedand their combined effects are unknown. In the present study, we investigated the toxic effectscaused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP andBPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed thatBPA did not reduce cell viability in HepG2 spheroids after 24-h exposure. In contrast, BPAP andBPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC)decreased cell viability in a dose-dependent manner, but the significant difference was only observedfor the combination of BPA/BPC (both at 40μM). After 96-h exposure, none of the BPs studiedaffected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cellviability in a dose-dependent manner that was significant for the combination of 4μM BPA and 4μMBPAP. None of the BPs and their binary mixtures studied affected the surface area and growth ofspheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggeredoxidative stress, as measured by the production of reactive oxygen species and malondialdehyde,at both exposure times. Overall, the results suggest that it is important to study the effects of BPsas single compounds. It is even more important to study the effects of combined exposures, as thecombined effects may differ from those induced by single compounds.
Keywords: BP analogues, hepatic in vitro 3D cell model, combined exposure, viability, oxidative stress, toxicology
Published in DiRROS: 12.07.2024; Views: 2; Downloads: 1
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2. Impact of deoxynivalenol and zearalenone as single and combined treatment on DNA, cell cycle and cell proliferation in HepG2 cellsAna-Marija Domijan, Klara Hercog, Martina Štampar, Goran Gajski, Marko Gerić, Marijana Sokolović, Bojana Žegura, 2023, original scientific article Abstract: The study aimed to investigate toxicity and the mechanism of toxicity of two Fusarium mycotoxins, deoxynivalenol (DON) and zearalenone (ZEA). DON and ZEA were applied to HepG2 cells as single compounds and in combination at low environmentally relevant concentrations. HepG2 cells were exposed to DON (0.5, 1, and 2 µM), ZEA (5, 10, and 20 µM) or their combinations (1 µM DON + 5 µM ZEA, 1 µM DON + 10 µM ZEA and 1 µM DON + 20 µM ZEA) for 24 h and cell viability, DNA damage, cell cycle and proliferation were assessed. Both mycotoxins reduced cell viability, however, combined treatment with DON and ZEA resulted in higher reduction of cell viability. DON (1 µM) induced primary DNA damage, while DON (1 µM) in combination with higher ZEA concentrations showed antagonistic effects compared to DON alone at 1 µM. DON arrested HepG2 cells in G2 phase and significantly inhibited cell proliferation, while ZEA had no significant effect on cell cycle. The combined treatment with DON and ZEA arrested cells in G2 phase to a higher extend compared to treatment with single mycotoxins. Potentiating effect observed after DON and ZEA co-exposure at environmentally relevant concentrations indicates that in risk assessment and setting governments’ regulations, mixtures of mycotoxins should be considered.
Keywords: mycotoxins, comet assay, flow cytometry, co-exposure, food monitoring
Published in DiRROS: 12.07.2024; Views: 22; Downloads: 3
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3. Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab : real-world experienceNežka Hribernik, Marko Boc, Janja Ocvirk, Jasna Knez Arbeiter, Tanja Mesti, Marija Ignjatović, Martina Reberšek, 2020, original scientific article Abstract: Based on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials. Patients and methods. This observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019. Results. The estimated median overall survival (OS) was 25.1 months (95% CI, 14.6%35.6) and the median progressionfree survival (PFS) was 10.7 months (95% CI, 5.9%15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3%4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment. Conclusions. Our real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.
Keywords: immunotherapy, pembrolizumab, metastatic melanoma, treatment-naive
Published in DiRROS: 11.07.2024; Views: 17; Downloads: 2
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4. A new perspective on the molecular dating of the stone crayfsh with an extended phylogeographic information on the speciesDavid Stanković, Katarina Zorić, Simona Đuretanović, Gorana Stamenković, Marija Ilić, Vanja Marković, Saša Marić, 2024, original scientific article Abstract: Reconstructing the origin and historical
biogeography of the Austropotamobius torrentium is
hampered by insufcient phylogeographic coverage
of the Balkans and deep contradictions in previous
molecular dating. The present work extends the phylogeographic coverage to Serbia, a country crucial for
understanding the species southward dispersal. Our
analysis revealed that the Southern Balkans lineage
occurs in most of the country, the Central and southeastern Europe lineage is restricted to the southwest
and northeast of the country, while a single population in the north of the country harbors the Lika and
Dalmatia lineage, which was previously thought to be
restricted to the northern-central Dinarides. Dataset
expansion led to revised phylogenetic relationships,
which indicated that the Apuseni lineage is not nested
within Northern-central Dinarides lineages but arose
after the most basal split within Austropotamobius
torrentium. This ‘Apuseni frst’ phylogeny provides
a new perspective for molecular dating, according to
which the split between Austropotamobius pallipes
and A. torrentium took place in the Late Oligocene,
while the formation of the phyletic lineages and the
dispersal from the Dinarides to Serbia occurred in
the late Miocene and is probably associated with the
complex and protracted process of disintegration of
the Neogene freshwater lakes in southeastern Europe.
Keywords: Austropotamobius torrentium, Austropotamobius bihariensis, divergence time estimation conficts, historical biogeography, neogene lakes, Serbia
Published in DiRROS: 09.07.2024; Views: 31; Downloads: 14
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5. Definitive radiochemotherapy in esophageal cancer : a single institution experienceFranc Anderluh, Miha Toplak, Vaneja Velenik, Irena Oblak, Ajra Šečerov Ermenc, Ana Jeromen, Jasna But-Hadžić, Marija Skoblar Vidmar, 2019, original scientific article Keywords: radiochemotherapy, definitive radiochemotherapy, esophageal cancer
Published in DiRROS: 05.07.2024; Views: 100; Downloads: 24
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6. Mobocertinib in patients with EGFR exon 20 insertion-positive non-small cell lung cancer (MOON) : an international real-world safety and efficacy analysisOliver Illini, Felix Carl Saalfeld, Petros Christopoulos, Michaël Duruisseaux, Anders Vikström, Nir Peled, Ingel Demedts, Elizabeth Dudnik, Anna Eisert, Urška Janžič, Katja Mohorčič, Marija Ivanović, Sayed M. S. Hashemi, 2024, original scientific article Abstract: EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
Keywords: medicina, non-small cell lung cancer, EGFR exon 20 inhibitors, mobocertinib, real-world data, exon 20 insertion
Published in DiRROS: 19.06.2024; Views: 99; Downloads: 63
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9. Mesenteric ischemia after capecitabine treatment in rectal cancer and resultant short bowel syndrome is not an absolute contraindication for radical oncological treatmentAna Perpar, Erik Brecelj, Nada Rotovnik-Kozjek, Franc Anderluh, Irena Oblak, Marija Skoblar Vidmar, Vaneja Velenik, 2015, other scientific articles Abstract: Thrombotic events, arterial or venous in origin, still remain a source of substantial morbidity and mortality in cancer patients. The propensity for their development in oncology patients is partially a consequence of the disease itself and partially a result of our attempts to treat it. One of the rarest and deadliest thromboembolic complications is arterial mesenteric ischemia. The high mortality rate is caused by its rarity and by its non-specific clinical presentation, both of which make early diagnosis and treatment difficult. Hence, most diagnoses and treatments occur late in the course of the disease. The issue survivors of arterial mesenteric ischemia may face is short bowel syndrome, which has become a chronic condition after the introduction of parenteral nutrition at home. We present a 73-year-old rectal cancer patient who developed acute arterial mesenteric thrombosis at the beginning of the pre-operative radiochemotherapy. Almost the entire length of his small intestine, except for the proximal 50 cm of it, and the ascending colon had to be resected. After multiorgan failure his condition improved, and he was able to successfully complete radical treatment (preoperative radiotherapy and surgery) for the rectal carcinoma, despite developing short bowel syndrome (SBS) and being dependent upon home-based parenteral nutrition to fully cover his nutritional needs. Mesenteric ischemia and resultant short bowel syndrome are not absolute contraindications for radical oncological treatment since such patients can still achieve long-term remission.
Keywords: acute mesenteric ischemia, capecitabine, multiorgan failure, rectal cancer, short bowel syndrome
Published in DiRROS: 23.04.2024; Views: 202; Downloads: 56
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10. Optimal scan time for evaluation of parathyroid adenoma with [18F]-fluorocholine PET/CTSebastijan Rep, Luka Ležaič, Tomaž Kocjan, Marija Pfeifer, Mojca Jensterle Sever, Urban Simončič, Petra Tomše, Marko Hočevar, 2015, original scientific article Keywords: lesions representing enlarged parathyroid tissue, triple-phase, standardized uptake value, retention index, lesion contrast, rak (medicina), obščitnični adenomi, diagnostika
Published in DiRROS: 22.04.2024; Views: 371; Downloads: 317
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