21. Abbreviated 13C-mixed triglyceride breath test for detection of pancreatic exocrine insufficiency performs equally as standard 5-hour test in patients after gastrectomy performed for gastric cancerDarko Siuka, Kristina Kumer, Borut Štabuc, David Štubljar, David Drobne, Rado Janša, 2022, izvirni znanstveni članek Ključne besede: abbreviated 13C-mixed triglyceride breath test, pancreatic exocrine insufficiency, gastrectomy, faecal elastase, gastric cancer
Objavljeno v DiRROS: 25.07.2024; Ogledov: 232; Prenosov: 46
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22. Real-world outcomes, treatment patterns and T790M testing rates in non-small cell lung cancer patients treated with first-line first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors from the Slovenian cohort of the REFLECT studyNina Turnšek, Rok Devjak, Natalija Edelbaher, Ilonka Osrajnik, Mojca Unk, Dušanka Vidovič, Tina Jerič, Urška Janžič, 2022, izvirni znanstveni članek Povzetek: Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). However, routine clinical practice is different between countries/institutions. Patients and methods. The REFLECT study (NCT04031898) is a retrospective medical chart review that explored real-life treatment and outcomes of EGFRm NSCLC patients receiving first-line (1L) first-/second-generation (1G/2G) EGFR TKIs in 8 countries. This study included adult patients with documented advanced/metastatic EGFRm NSCLC with 1L 1G/2G EGFR TKIs initiated between Jan 2015 – Jun 2018. We reviewed data on clinical characteristics, treatments, EGFR/T790M testing patterns, and survival outcomes. Here, we report data from 120 medical charts in 3 study sites from Slovenia. Results. The Slovenian cohort (median age 70 years, 74% females) received 37% erlotinib, 32% afatinib, 31% gefitinib. At the time of data collection, 94 (78%) discontinuations of 1L TKI, and 89 (74%) progression events on 1L treatment were reported. Among patients progressing on 1L, 73 (82%) were tested for T790M mutation yielding 50 (68%) positive results, and 62 (85%) received 2L treatment. 82% of patients received osimertinib. Attrition rate between 1L and 2L was 10%. The median (95% CI) real-world progression free survival on 1L EGFR TKIs was 15.6 (12.6, 19.2) months; median overall survival (95% CI) was 28.9 (25.0, 34.3) months. Conclusions. This real-world study provides valuable information about 1G/2G EGFR TKIs treatment outcomes and attrition rates in Slovenian EGFRm NSCLC patients. The reduced attrition rate and improved survival outcomes empha-size the importance of 1L treatment decision.
Ključne besede: real-world study, non-small cell lung cancer, epidermal growth factor receptor, lung cancer
Objavljeno v DiRROS: 25.07.2024; Ogledov: 110; Prenosov: 49
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24. Identification of women with high grade histopathology results after conisation by artificial neural networksMarko Mlinarič, Miljenko Križmarić, Iztok Takač, Alenka Repše-Fokter, 2022, izvirni znanstveni članek Povzetek: Background: The aim of the study was to evaluate if artificial neural networks can predict high-grade histopathology results after conisation from risk factors and their combinations in patients undergoing conisation because of pathological changes on uterine cervix. Patients and methods: We analysed 1475 patients who had conisation surgery at the University Clinic for Gynaecology and Obstetrics of University Clinical Centre Maribor from 1993-2005. The database in different datasets was arranged to deal with unbalance data and enhance classification performance. Weka open-source software was used for analysis with artificial neural networks. Last Papanicolaou smear (PAP) and risk factors for development of cervical dysplasia and carcinoma were used as input and high-grade dysplasia Yes/No as output result. 10-fold cross validation was used for defining training and holdout set for analysis. Results: Baseline classification and multiple runs of artificial neural network on various risk factors settings were performed. We achieved 84.19% correct classifications, area under the curve 0.87, kappa 0.64, F-measure 0.884 and Matthews correlation coefficient (MCC) 0.640 in model, where baseline prediction was 69.79%. Conclusions: With artificial neural networks we were able to identify more patients who developed high-grade squamous intraepithelial lesion on final histopathology result of conisation as with baseline prediction. But, characteristics of 1475 patients who had conisation in years 1993-2005 at the University Clinical Centre Maribor did not allow reliable prediction with artificial neural networks for every-day clinical practice.
Ključne besede: artificial neural networks, conisation, uterine cervical cancer, uterine cervical dysplasia, displazija materničnega vratu, rak materničnega vratu, konizacija, umetne nevronske mreže
Objavljeno v DiRROS: 24.07.2024; Ogledov: 107; Prenosov: 74
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25. Ribociclib plus letrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer with no prior endocrine therapy : subgroup safety analysis from the phase 3b CompLEEment-1 trialSimona Borštnar, Marketa Palacova, Aleksandra Łacko, Constanta Timcheva, Einav Nili Gal-Yam, Konstantinos Papazisis, Juraj Beniak, Pavol Kudela, Gábor Rubovszky, 2022, izvirni znanstveni članek Povzetek: The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1. Patients and methods: Men and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured. Results: Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events. Conclusions: These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice.
Ključne besede: CDK4/6 inhibitor, HER2−, HR+, advanced breast cancer, ribociclib
Objavljeno v DiRROS: 24.07.2024; Ogledov: 103; Prenosov: 178
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26. Sunitinib potentiates the cytotoxic effect of electrochemotherapy in pancreatic carcinoma cellsMaša Omerzel, Tanja Jesenko, Boštjan Markelc, Anja Cerovšek, Gregor Serša, Maja Čemažar, 2022, izvirni znanstveni članek Povzetek: One of the new treatment options for unresectable locally advanced pancreatic cancer is electro-chemotherapy (ECT), a local ablative therapy that potentiates the entry of chemotherapeutic drugs into the cells, by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice. Materials and methods. The aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death.Results. The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used, with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treat-ment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity. The combined treatment of sunitinib and ECT was synergistic for bleomycin only at the high-est used concentration of bleomycin 0.14 μM, whereas with lower doses of bleomycin, this effect was not observed. The interaction of ECT and treatment with sunitinib was confirmed by course of the cell death, also indicating on synergism
Ključne besede: electrochemotherapy, pancreas, sunitinib, pancreatic cancer
Objavljeno v DiRROS: 24.07.2024; Ogledov: 122; Prenosov: 82
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27. Expression of DNA-damage response and repair genes after exposure to DNA-damaging agents in isogenic head and neck cells with altered radiosensitivityVesna Todorović, Blaž Grošelj, Maja Čemažar, Ajda Prevc, Martina Nikšić Žakelj, Primož Strojan, Gregor Serša, 2022, izvirni znanstveni članek Povzetek: Background: Increased radioresistance due to previous irradiation or radiosensitivity due to human papilloma virus (HPV) infection can be observed in head and neck squamous cell carcinoma (HNSCC). The DNA-damage response of cells after exposure to DNA-damaging agents plays a crucial role in determining the fate of exposed cells. Tightly regulated and interconnected signaling networks are activated to detect, signal the presence of and repair the DNA damage. Novel therapies targeting the DNA-damage response are emerging; however, an improved understanding of the complex signaling networks involved in tumor radioresistance and radiosensitivity is needed. Materials and methods: In this study, we exposed isogenic human HNSCC cell lines with altered radiosensitivity to DNA-damaging agents: radiation, cisplatin and bleomycin. We investigated transcriptional alterations in the DNA-damage response by using a pathway-focused panel and reverse-transcription quantitative PCR. Results: In general, the isogenic cell lines with altered radiosensitivity significantly differed from one another in the expression of genes involved in the DNA-damage response. The radiosensitive (HPV-positive) cells showed overall decreases in the expression levels of the studied genes. In parental cells, upregulation of DNA-damage signaling and repair genes was observed following exposure to DNA-damaging agents, especially radiation. In contrast, radioresistant cells exhibited a distinct pattern of gene downregulation after exposure to cisplatin, whereas the levels in parental cells were unchanged. Exposure of radioresistant cells to bleomycin did not significantly affect the expression of DNA-damage signaling and repair genes. Conclusions: Our analysis identified several possible targets: NBN, XRCC3, ATR, GADD45A and XPA. These putative targets should be studied and potentially exploited for sensibilization to ionizing radiation and/or cisplatin in HNSCC. The use of predesigned panels of DNA-damage signaling and repair genes proved to offer a convenient and quick approach to identify possible therapeutic targets.
Ključne besede: DNA-damaging agents, gene expression, head and neck cancer, squamous cell carcinoma
Objavljeno v DiRROS: 24.07.2024; Ogledov: 135; Prenosov: 96
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28. Localization patterns of cathepsins K and X and their predictive value in glioblastomaBarbara Breznik, Clara Limbaeck Stanic, Andrej Porčnik, Andrej Blejec, Miha Koprivnikar Krajnc, Roman Bošnjak, Janko Kos, Cornelis J. F. van Noorden, Tamara Lah Turnšek, 2018, izvirni znanstveni članek Povzetek: Background
Glioblastoma is a highly aggressive central nervous system neoplasm characterized by extensive infiltration of malignant cells into brain parenchyma, thus preventing complete tumor eradication. Cysteine cathepsins B, S, L and K are involved in cancer progression and are overexpressed in glioblastoma. We report here for the first time that cathepsin X mRNA and protein are also abundantly present in malignant glioma.
Materials and methods
Gene expression of cathepsins K and X was analyzed using publically-available tran-scriptomic datasets and correlated with glioma grade and glioblastoma subtype. Kaplan-Maier survival analysis was performed to evaluate the predictive value of cathepsin K and X mRNA expression. Cathepsin protein expression was localized and semi-quantified in tumor tissues by immunohistochemistry.
Results
Highest gene expression of cathepsins K and X was found in glioblastoma, in particular in the mesenchymal subtype. Overall, high mRNA expression of cathepsin X, but not that of cathepsin K, correlated with poor patients’ survival. Cathepsin K and X proteins were abundantly and heterogeneously expressed in glioblastoma tissue. Immuno-labeling of cathepsins K and X was observed in areas of CD133-positive glioblastoma stem cells, localized around arterioles in their niches that also expressed SDF-1α and CD68. mRNA levels of both cathepsins K and X correlated with mRNA levels of markers of glioblastoma stem cells and their niches.
Conclusions
The presence of both cathepsins in glioblastoma stem cell niche regions indicates their possible role in regulation of glioblastoma stem cell homing in their niches. The clinical relevance of this data needs to be elaborated in further prospective studies.
Ključne besede: cathepsins, glioblastoma, immunohistochemistry, patient survival, cancer stem cell niches
Objavljeno v DiRROS: 24.07.2024; Ogledov: 145; Prenosov: 105
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29. Maristem - stem cells of marine/aquatic invertebrates : from basic research to innovative applicationsLoriano Ballarin, Baruch Rinkevich, Kestin Bartscherer, Artur Burzynski, Sebastien Cambier, Matteo Cammarata, Isabelle Domart-Coulon, Damjana Drobne, Juanma Encinas, Uri Frank, Anne-Marie Geneviere, Bert Hobmayer, Helike Löhelaid, Daniel Lyons, Pedro Martinez, Paola Oliveri, Lorena Perić, Stefano Piraino, Andreja Ramšak, Sebastian Rakers, Fabian Rentzsch, Amalia Rosner, Tiago Henriques da Silva, Ildiko Somorjai, Sherif Suleiman, Ana Varela Coelho, 2018, izvirni znanstveni članek Povzetek: The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, and zebrafish) and invertebrate (e.g., Drosophila, Caenorhabditis) models have not been pursued vigorously. Marine/aquatic invertebrates constitute the largest biodiversity and the widest phylogenetic radiation on Earth, from morphologically simple organisms (e.g., sponges, cnidarians), to the more complex mollusks, crustaceans, echinoderms, and protochordates. These organisms contain a kaleidoscope of MISC-types that allow the production of a large number of novel bioactive-molecules, many of which are of significant potential interest for human health. MISCs further participate in aging and regeneration phenomena, including whole-body regeneration. For years, the European MISC-community has been highly fragmented and has established scarce ties with biomedical industries in an attempt to harness MISCs for human welfare. Thus, it is important to (i) consolidate the European community of researchers working on MISCs; (ii) promote and coordinate European research on MISC biology; (iii) stimulate young researchers to embark on research in MISC-biology; (iv) develop, validate, and share novel MISC tools and methodologies; (v) establish the MISC discipline as a forefront interest of biomedical disciplines, including nanobiomedicine; and (vi) establish collaborations with industries to exploit MISCs as sources of bioactive molecules. In order to fill the recognized gaps, the EC-COST Action 16203 “MARISTEM” has recently been launched. At its initial stage, the consortium unites 26 scientists from EC countries, Cooperating countries, and Near Neighbor Countries.
Ključne besede: aging, bioactive molecules, blue biotechnology, cancer, cell culture, COST Action, Europe, marine/aquatic invertebrates, regeneration, stem cells
Objavljeno v DiRROS: 24.07.2024; Ogledov: 321; Prenosov: 97
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30. A simple in silico approach to generate gene-expression profiles from subsets of cancer genomics dataMohammed Khurshed, Remco J. Molenaar, Cornelis J. F. van Noorden, 2019, izvirni znanstveni članek Povzetek: In biomedical research, large-scale profiling of gene expression has become routine and offers a valuable means to evaluate changes in onset and progression of diseases, in particular cancer. An overwhelming amount of cancer genomics data has become publicly available, and the complexity of these data makes it a challenge to perform in silico data exploration, integration and analysis, in particular for scientists lacking a background in computational programming or informatics. Many web interface tools make these large datasets accessible but are limited to process large datasets. To accelerate the translation of genomic data into new insights, we provide a simple method to explore and select data from cancer genomic datasets to generate gene-expression profiles of subsets that are of specific genetic, biological or clinical interest.
Ključne besede: cancer genomics, cBioPortal, data mining, epigenetics, gene expression, in silico
Objavljeno v DiRROS: 24.07.2024; Ogledov: 218; Prenosov: 451
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