1. Evaluation of the training program for p16/ Ki-67 dual immunocytochemical staining interpretation for laboratory staff without experience in cervical cytology and immunocytochemistryVeronika Kloboves-Prevodnik, Živa Pohar-Marinšek, Janja Zalar, Hermina Rozina, Nika Kotnik, Tine Jerman, Jerneja Varl, Urška Ivanuš, 2020, original scientific article Abstract: ackground p16/Ki-67 dual immunocytochemical staining (DS) is considered easy to interpret if evaluators are properly trained, however, there is no consensus on what constitutes proper training. In the present study we evaluated a protocol for teaching DS evaluation on students inexperienced in cervical cytology. Methods Initial training on 40 DS conventional smears was provided by a senior cytotechnologist experienced in such evaluation. Afterwards, two students evaluated 118 cases. Additional training consisted mainly of discussing discrepant cases from the first evaluation and was followed by evaluation of new 383 cases. Agreement and accuracy of students' results were compared among the participants and to the results of the reference after both evaluations. We also noted time needed for evaluation of one slide as well as intra-observer variability of the teacher's results. Results At the end of the study, agreement between students and reference was higher compared to those after initial training (overall percent agreement [OPA] 81.4% for each student, kappa 0.512 and 0.527 vs. OPA 78.3% and 87.2%, kappa 0.556 and 0.713, respectively). However, accuracy results differed between the two students. After initial training sensitivity was 4.3% points and 2.9% points higher, respectively compared to the reference, while specificity was 30.6% points and 24.4% points lower, respectively, compared to the reference. At the end of the study, the sensitivity reached by one student was the same as that of the reference, while it was 2.6% points lower for the other student. There was a statistically significant difference in specificity between one student and the reference and also between students (16.7 and 15.1% points). Towards the end of the study, one student needed 5.2 min for evaluating one slide while the other needed 8.2 min. The intra-observer variability of the senior cytotechnologist was in the range of "very good" in both arms of the study. Conclusions In teaching DS evaluation, the students' progress has to be monitored using several criteria like agreement, accuracy and time needed for evaluating one slide. The monitoring process has to continue for a while after students reach satisfactory results in order to assure a continuous good performance. Monitoring of teacher's performance is also advisable.
Keywords: cervical cytology, cervical cancer, immunocytochemistry, accuracy
Published in DiRROS: 11.07.2024; Views: 4; Downloads: 4
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2. Molecular heterogeneity in breast carcinoma cells with increased invasive capacitiesGiulia Negro, Bertram Aschenbrenner, Simona Kranjc Brezar, Maja Čemažar, Andrej Cör, Gorana Gašljević, Maxim Sorokin, Anton A. Buzdin, Maurizio Callari, Irma Kvitsaridze, 2020, original scientific article Abstract: Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes. Materials and methods. In order to reach this aim, parental and invasive (INV) MDA-MB-231 (triple-negative), T47D (hormone receptor-positive), and Au565 (Her2-positive) breast carcinoma cells were used and their molecular phenotypes were compared using a proteomic approach. Results. Independently from breast cancer subtypes, INV cells have demonstrated fibroblast-like morphology accompanied by enhancement of invasive and migratory capacities, increased expression of cancer stem cell markers, and delayed tumor growth in in vivo animal models. However, the global proteomic analysis has highlighted that INV cells were different in protein expressions from the parental cells, and Her2-positive Au565-INV cells showed the most pronounced molecular differences compared to the triple-negative MDA-MB-231-INV and hormone receptor-positive T47D-INV cells. Although Au565-INV breast carcinoma cells possessed the highest number of deregulated proteins, they had the lowest overlapping in proteins commonly expressed in MDA-MB-231-INV and T47D-INV cells. Conclusions. We can conclude that hormone receptor-positive cells with increased invasiveness acquire the molecular characteristics of triple-negative breast cancer cells, whereas Her2-positive INV cells specifically changed their own molecular phenotype with very limited partaking in the involved pathways found in the MDA-MB-231-INV and T47D-INV cells. Since hormone receptor-positive invasive cells share their molecular properties with triple-negative breast cancer cells, we assume that these types of metastatic disease can be treated rather equally with an option to add anti-hormonal agents. In contrast, Her2-positive metastasis should be carefully evaluated for more effective therapeutic approaches which are distinct from the triple-negative and hormone-positive metastatic breast cancers.
Keywords: breast cancer, cancer stem cells, invasiveness, migration, metastasis
Published in DiRROS: 11.07.2024; Views: 4; Downloads: 2
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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: 10; Downloads: 2
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4. Influence of alkylthio and arylthio derivatives of tert-butylquinone on the induction of DNA damage in a human hepatocellular carcinoma cell line (HepG2)Jelena Djordjević, Stoimir Kolarević, Jovana Jovanović Marić, Margareta Kračun-Kolarević, Bojana Žegura, Alja Štern, Dušan M. Sladić, Irena Novaković, Branka Vuković-Gačić, 2024, original scientific article Abstract: The aim of this study was to investigate the effects of tert-butylquinone (TBQ) and its alkylthio and arylthio
derivatives on DNA in vitro, using acellular and cellular test systems. Direct interaction with DNA was studied
using the plasmid pUC19. Cytotoxic (MTS assay) and genotoxic (comet assay and γH2AX focus assays) effects,
and their influence on the cell cycle were studied in the HepG2 cell line. Our results show that TBQ and its
derivatives did not directly interact with DNA. The strongest cytotoxic effect on the HepG2 cells was observed for
the derivative 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone (IC50 64.68 and 55.64 μM at 24-h and 48-h
treatment, respectively). The tested derivatives did not significantly influence the cell cycle distribution in the
exposed cellular populations. However, all derivatives showed a genotoxic activity stronger than that of TBQ in
the comet assay, with 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone producing the strongest effect. The
same derivative also induced DNA double-strand breaks in the γH2AX focus assay.
Keywords: TBQ derivatives, HepG2 cell line, comet assay, γH2AX assay, cell cycle analysis, cytotoxicity
Published in DiRROS: 11.07.2024; Views: 5; Downloads: 7
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5. Phytoplankton assemblage over a 14-year period in the Adriatic Sea : patterns and trendsSanda Skejić, Blanka Milić Roje, Frano Matić, Jasna Arapov, Janja Francé, Mia Bužančić, Ana Bakrač, Maja Straka, Živana Ninčević Gladan, 2024, original scientific article Abstract: Considering the role of phytoplankton in the functioning and health of marine systems, it is important to characterize its responses to a changing environment. The central Adriatic Sea, as a generally oligotrophic area, is a suitable environment to distinguish between regular fluctuations in phytoplankton and those caused by anthropogenic or climatic influences. This study provides a long-term perspective of phytoplankton assemblage in the central eastern Adriatic Sea, with 14 years of continuous time series data collected at two coastal and two offshore stations. The predominant phytoplankton groups were diatoms and phytoflagellates, but their proportion varied depending on the vicinity of the coast, as evidenced also by the distribution of chlorophyll a. In the coastal environment, the phytoplankton biomass was substantially higher, with a higher proportion of microphytoplankton, while small phytoplankton accounted for the majority of biomass in the offshore area. In addition, a decreasing trend in diatom abundance was observed in the coastal waters, while such trend was not so evident in the offshore area. Using a neural gas algorithm, five clusters were defined based on the contribution of the major groups. The observed increase in diversity, especially in dinoflagellates, which outnumber diatom taxa, could be a possible adaptation of dinoflagellates to the increased natural solar radiation in summer and the increased sea surface temperature.
Keywords: phytoplankton community, long-term data, diversity, chlorophyll a, neural gas analysis, solar radiation, Adriatic Sea
Published in DiRROS: 11.07.2024; Views: 7; Downloads: 5
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7. Oral bioaccessibility of potentially toxic elements in various environmental mediaMartin Gaberšek, Mateja Gosar, 2024, original scientific article Abstract: An important aspect of geochemical studies is determining health hazard of potentially toxic elements (PTEs). Key information on PTEs behaviour in the human body in case of their ingestion is provided with the use of in vitro bioaccessibility tests. We analysed and compared oral bioaccessibility of a wide range of PTEs (As, Cd, Ce, Cr, Cu, Hg, La, Li, Ni, Pb, Sb, Sn, Zn), including some that are not often studied but might pose a human health hazard, in soil, attic dust, street dust, and household dust, using Unified BARGE Method (UBM). Additionally, feasibility of usage of scanning electron microscope techniques in analyses of solid residuals of UBM phases was tested. Results show that bioaccessible fractions (BAFs) of PTEs vary significantly between individual samples of the same medium, between different media and between the gastric and gastro-intestinal phases. In soil, attic dust and street dust, bioaccessibility of individual PTE is mostly higher in gastric than in gastro-intestinal phase. The opposite is true for PTEs in household dust. In all four media, with the exception of Pb in household dust, among the most bioaccessible PTEs in gastric phase are Cd, Cu, Pb, and Zn. During the transition from the stomach to small intestine, the mean BAFs of most elements in soil, attic dust, and street dust decreases. The most bioaccessible PTEs in gastro-intestinal phase are Cu, Cd, Ni, and As. Micromorphological and chemical characterisation at individual particle level before and after bioaccessibility test contribute significantly to the understanding of oral bioaccessibility.
Keywords: urban geochemistry, UBM, soil, attic dust, street dust, household dust
Published in DiRROS: 10.07.2024; Views: 29; Downloads: 9
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8. Synergetic boost of functional properties near critical end points in antiferroelectric systemsVida Jurečič, Lovro Fulanović, Jurij Koruza, Vid Bobnar, Nikola Novak, 2023, original scientific article Abstract: The increase of the dielectric permittivity with an electric field and enhanced energy storage properties make antiferroelectrics very attractive for high-power electronic applications needed in emerging green energy technologies and neuromorphic computing platforms. Their exceptional functional properties are closely related to the electric field-induced antiferroelectric↔ferroelectric phase transition, which can be driven toward a critical end point by manipulation with an external electric field. The critical fluctuation of physical properties at the critical end point in ferroelectrics is a promising approach to improve their functional properties. Here, we demonstrate the existence of two critical end points in antiferroelectric ceramics with a ferroelectric-antiferroelectric-paraelectric phase sequence, using the model system Pb 0.99 Nb 0.02 [ ( Zr 0.57 Sn 0.43 ) 0.92 Ti 0.08 ] 0.98 O 3 . The critical fluctuation of the dielectric permittivity in the proximity of the antiferroelectric-to-paraelectric critical end point is responsible for the strong enhancement of the dielectric tunability (by a factor of > 2 ) measured at ≈ 395 K. The enhancement of the energy storage density at ≈ 370 K is related to the proximity of the ferroelectric-to-antiferroelectric critical end point. These findings open possibilities for material design and pave the way for the next generation of high-energy storage materials.
Keywords: electronic applications, high-power electronic, green energy, electric field
Published in DiRROS: 10.07.2024; Views: 27; Downloads: 23
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